Abstract：Traditional Chinese medicine has become an important means of combined Chinese and Western medicine treatment for gastric cancer due to its unique advantages of multi-target, multi-pathway and low toxicity.In recent years, it has been found that traditional Chinese medicines (TCM) such as Fu Zheng class, transforming phlegm and softening hardness, activating blood circulation and removing blood stasis, regulating qi and harmonising the stomach, clearing heat and removing toxins, and combating toxins with toxins can play a therapeutic role in treating gastric cancer by acting on multiple targets in the process of gastric cancer occurrence and development, regulating related molecular mechanisms and remodelling the immune microenvironment, for instance, Eugenol can inhibit epithelial-mesenchymal transformation of gastric cancer cells by down-regulating the expression of TGF-β, and blocking the nuclear translocation of the SMAD3/SMAD4 complex;Atractylenolide II can promote macrophage polarisation to M1 type by inhibiting PI3K phosphorylation.By integrating and elucidating the latest research results, this paper is expected to lay the foundation of translational medicine for the development of combined Chinese and Western medicine strategies for the precision treatment of gastric cancer.
胃癌因其早期临床症状隐匿，导致大多数患者在确诊时已进展至晚期阶段[1]。我国胃癌患者的五年总生存率仅为35.1%[2]。值得关注的是，低毒性的传统中医药，凭借其多靶点、多途径的调控优势，已在胃癌综合治疗体系中确立协同治疗地位。《胃癌中西医结合诊疗指南》的循证医学证据也表明，中医药与放化疗联合治疗有助于改善胃癌预后和减少不良反应（详见表1）[3-11]。因此，本文系统综述了近年来研究报道的扶正类、化痰软坚类、活血化瘀类、理气和胃类、清热解毒类及以毒攻毒类中医药治疗胃癌的作用靶点、分子机制及对免疫微环境重塑的影响，旨在为中医药在胃癌个性化治疗体系中的临床应用奠定理论基础。
表1 治疗胃癌的中医药
1 中医药治疗胃癌的分子机制
研究发现：扶正类、化痰软坚类、活血化瘀类、理气和胃类、清热解毒类和以毒攻毒类中医药可通过诱导胃癌细胞凋亡[12-23]、调控其周期[20, 24-33]、逆转其上皮间充质转化[34-39]、抑制其血管生成[40-45]来治疗胃癌（详见图1、图2、表2）。
虚线左侧：死亡受体途径（Death receptor pathway）：上调FAS表达（橘黄色框）：Del、CuL、Iri。上调FADD表达（深绿色框）：Cul。虚线右侧：线粒体途径（Mitochondrial pathway）：下调Bcl-2和上调Bax表达（深红色框）：Sal、Cin、Nob、Cel、Ber。下调Bcl-2表达（深蓝色框）：Ole。上调Bid表达（浅绿色框）：SOD。激活caspase-9（浅蓝色框）：SA。激活Caspase-3（浅红色框）：Eria。备注:红色字:扶正类：红景天苷 Sal、桂皮醛 Cin、三角叶薯蓣皂苷 Del、毛兰素 Eria是红景天、肉桂皮、盾叶薯蓣、石斛的有效成分；黄色字：化痰软坚类:川陈皮素 Nob、五味子酯甲 SA是陈皮、五味子的有效成分；白色字：活血化瘀类：柘树酮L CuL、雷公藤红素 Cel是柘树、雷公藤的有效成分；浅蓝色字：理气和胃类：橄榄苦苷 Ole是橄榄的有效成分；紫色字：清热解毒类：野鸢尾苷 Iri、槐定碱 SOD、黄连素 Ber是射干、苦豆子、黄连的有效成分；橘黄色字：以毒攻毒类：芫花瑞香素Gen是芫花的有效成分。
图1 中医药促进胃癌细胞凋亡的机制
G0/G1期（红/黄色区）：JAC下调CDK4/6、Cyclin D1、Cyclin E表达。G1期（红/黄色区）Gar、CEP、GTE分别下调Cyclin D1表达、下调Cyclin D1和CDK2表达、下调CDK2/Cyclin E复合物表达。G1/S期（红/黄色区）：GLA下调Cyclin D1、E1表达。S/G2期（红/绿/蓝色区）：Mag、Alo分别下调Cyclin A表达、下调Cyclin D1表达。G2/M期（紫色区）：Res、Ger、Iri/Api分别使CDK1/Cyclin B1复合物失活、下调Cyclin B1表达、下调CDK1和Cyclin B1表达。备注：红色字：扶正类：甘草酸 GLA是甘草的有效成分；蓝色字：活血化瘀类：山竹子素 Gar、白藜芦醇 Res、吉马酮 Ger是藤黄、虎杖、莪术的有效成分；紫色字：理气和胃类：棕矢车菊素JAC是艾叶的有效成分；绿色字：清热解毒类：木兰花碱Mag、芦荟素Alo、千金藤素 CEP、野鸢尾苷 Iri、芹菜苷 Api是黄连、芦荟、头花蓼、射干、半枝莲的有效成分和老鹳草提取物GTE。
图2 中医药调控CDKs和Cyclins,诱发胃癌细胞周期阻滞的机制
表2 抑制胃癌上皮间充质转化和血管生成的中医药及有效成分
1.1 中医药调控MAPK信号通路 高表达的pERK是胃癌不良预后的独立预测因子[46]。敲除JNK基因可显著减少小鼠胃癌发生率[47]。通过激活AP-1通路，p38可增强胃癌化疗耐药性[48]。研究发现：ⅰ）扶正类：甘草的萜类成分：甘草次酸（GRA）可通过抑制RAS磷酸化，抑制胃癌细胞增殖[49]。毛蕊异黄酮（Cal）、竹荪多糖（DRP）作为黄芪、竹荪的黄酮类、多糖成分，和白术提取物（AMKE）、胃复春（WFC）均可通过调控p38、JNK和ERK磷酸化，诱导胃癌细胞凋亡[50-53]。ⅱ）化痰软坚类：香连丸（XLP）由余黄连和木香组成，可促进p38磷酸化，进而增强5-FU对胃癌的杀伤活性[54]。ⅲ）活血化瘀类:龙血竭乙酸乙酯提取物（CDBEE）可通过促进ERK、p38和JNK磷酸化，抑制胃癌细胞生长[55]。藏红花素（Cro）、异鼠李素（IH）是藏红花的类胡萝卜素、黄酮类成分，可分别通过下调FGFR3、p38表达，抑制胃癌细胞EMT或侵袭[56, 57]。ⅳ）理气和胃类：芍药、艾叶的活性成分：芍药苷（PF）、棕矢车菊素（JAC），可分别通过下调RAS表达、调控p38、JNK和ERK磷酸化，抑制胃癌细胞转移或诱导其凋亡[28, 58]。ⅴ）清热解毒类：大黄的蒽醌类成分：大黄酸（Rhe）可通过促进p38磷酸化，诱导胃癌细胞凋亡[59]。木兰花碱（Mag）、小檗碱（BBR）是黄连的生物碱成分，可分别通过促进JNK磷酸化、抑制ERK、JNK、p38磷酸化，阻滞胃癌细胞于S/G2期或诱导其发生静态自噬[29, 60]（详见图3）。
The ERK Pathway（左上区）:促进ERK磷酸化（蓝色框）：CDBEE；抑制ERK磷酸化（红色框）：Cal、AMKE、DRP、WEC、JAC、BBR；下调FGFR3表达（绿色框）：Cro；抑制RAS磷酸化（黄色框）：GRA；下调RAS表达（紫色框）:PF。The P38 Pathway（右上区）：抑制p38磷酸化（红色框）：DRP、WFC、Mag、BBR；促进p38磷酸化（蓝色框）：Cal、AMKE、XLP、CDBEE、JAC、Rhe；下调p38表达（橘黄色框）：IH。The JNK Pathway（正下区）：促进JNK磷酸化（蓝色框）：CDBEE、JAC、Mag；抑制JNK磷酸化（红色框）：DRP、BBR。备注：红色字：扶正类；黄色字：化痰软坚类；蓝色字：活血化瘀类；绿色字：理气和胃类；紫色字：清热解毒类。
图3 中医药调控胃癌MAPK信号通路的机制
1.2 中医药调控PI3K/AKT信号通路 PIK3CA的扩增可导致pAKT表达升高，进而促进胃癌淋巴结转移[61]。mTOR的高表达也与胃癌浸润深度呈正相关[62]。研究发现：ⅰ）扶正类：红景天的苯乙醇苷类成分：红景天苷（Sal）可分别通过抑制PI3K和AKT磷酸化、抑制mTOR磷酸化，诱导胃癌细胞凋亡或促进其自噬[13]。红参多糖（RGP）、汉防己甲素（TET）分别是红参、粉防己的多糖、生物碱类成分，均可通过抑制PI3K、AKT磷酸化，诱导胃癌细胞铁死亡或抑制其侵袭[63, 64]。滋阴化痰方（ZYHTR）由百合、半夏等组成，可通过降低PI3K表达，促进胃癌细胞凋亡[65]。当归四逆汤（DSD）、健脾养胃方（JPYW）均可通过抑制AKT磷酸化，阻滞胃癌细胞于G2/M期或促进5-FU耐药胃癌细胞凋亡[66, 67]。芪苓汤（QLDn）由黄芪、半枝莲等组成，可通过下调PI3K和AKT表达，抑制胃癌细胞转移[68]。ⅱ）化痰软坚类：芫菁科昆虫的萜类成分：斑蝥素（CTD）可通过增高PTEN表达和降低AKT表达，抑制胃癌细胞转移[69]。ⅲ）活血化瘀类：水红花子的黄酮类成分:圣草酚（Eri）可通过抑制PI3K和AKT磷酸化，诱导胃癌细胞凋亡[70]。 ⅳ）清热解毒类：芦荟的蒽醌类成分:芦荟素（Aloin）可通过降低PI3K和AKT表达，诱导胃癌细胞凋亡[71]。金合欢素（ACA）是野菊的黄酮类成分，可通过抑制PI3K和AKT磷酸化，抑制胃癌细胞EMT[37]。复方苦参注射液（CKI）由苦参和土茯苓组成，可通过降低pAKT和PI3K表达，抑制胃癌细胞EMT[38]（详见图4）。
1.3 中医药调控JAK/STAT信号通路 STAT3的表达与胃癌的分化程度密切相关。研究发现：ⅰ）扶正类：绞股蓝的皂苷类成分:绞股蓝皂苷（Gyp）可通过抑制STAT3磷酸化，下调胃癌细胞上PD-L1表达，进而增强T细胞抗肿瘤活性[72]。甘草泻心汤（GCXXD）由甘草、黄芩等组成，可通过抑制JAK2、STAT3表达及磷酸化，抑制胃癌细胞迁移[73]。ⅱ）活血化瘀类：姜黄的酚类成分：姜黄素（Cur）可通过抑制STAT3磷酸化，减弱胃癌细胞对5-FU的耐药性[74]。ⅲ）理气和胃类:薄荷的萜类成分：右旋香芹酮（D-Car）可通过抑制STAT3磷酸化，诱导胃癌细胞凋亡[50]。ⅳ）清热解毒类：黄连的生物碱成分：小檗碱（BBR）可通过促进JAK2、STAT3磷酸化，阻滞胃癌细胞于G0/G1期[22]。其与姜黄素联用则可通过抑制STAT3磷酸化，诱导胃癌细胞凋亡[49]。重楼皂苷I（PI）是重楼的皂苷类成分，与漆树提取物（RVSE）均可通过抑制STAT3磷酸化，诱导胃癌细胞凋亡或抑制其转移[52, 75]（详见图4）。
1.4 中医药调控NF-κB信号通路 NF-κB通路的异常激活可加速胃癌进展[76]。研究发现：ⅰ）扶正类：扶正活胃汤的倍半萜类成分：莪术醇（Curc）与复方消癌肥蜜膏（CXHO）均可通过抑制p65表达及磷酸化，抑制胃癌细胞侵袭或迁移[77, 78]。ⅱ）化痰软坚类：夏枯草的萜类成分：熊果酸（UA）可分别通过抑制p65磷酸化、抑制IKKα/β磷酸化，抑制胃癌细胞的炎症反应或EMT[79, 80]。ⅲ）活血化瘀类：龙葵的生物碱成分：澳洲茄胺（SOL）可通过抑制p65核转位，抑制胃癌细胞EMT[81]。ⅳ）清热解毒类：筋骨草的黄酮类成分：香叶木素（DIO）可通过抑制p65磷酸化，阻遏TAMs向M2型极化，进而抑制胃癌细胞侵袭[82]。ⅴ）以毒攻毒类：鸦旦子的内酯成分：鸦胆子苦醇（Bru）可通过下调p65表达，逆转胃癌细胞EMT[83]（详见图4）。
1.5 中医药调控NOTCH信号通路 NOTCH1 mRNA的高表达与患者较短的总生存期呈正相关[84]。研究发现：ⅰ）扶正类：白术的倍半萜烯成分：白术内酯Ⅰ（AT-Ⅰ）既可通过下调JAG1表达，抑制胃癌细胞增殖，又可通过下调NOTCH1表达，抑制GCSLCs自我更新[85]。ⅱ）清热解毒类：金银花的黄酮类成分：木犀草素（Lut）可通过下调NOTCH1表达，逆转胃癌细胞EMT[86]。ⅲ）活血化瘀类：雷公藤的萜类成分：雷公藤内酯酮（Tri）可通过泛素化降解NOTCH1，抑制胃癌细胞转移[87]。ⅳ）化痰软坚类：郁金的活性成分：β-二甲基丙烯酰紫草素（DA）和β-榄香烯（β-El）均可下调NOTCH1表达，进而诱导胃癌凋亡或减弱其血管生成[88, 89]。消痰散结方（XTSJ）由半夏、南星等组成，可通过下调NOTCH1表达，抑制胃癌血管生成[90]（详见图4）。
The NF-κB Pathway（左上区）：抑制IKKα/β磷酸化（深棕色框）：UA;下调p65表达（粉红色框）：Curc、CXHO、Bru；抑制p65磷酸化（橘黄色框）：Curc、CXHO、DIO、UA；抑制p65核转位（深蓝色框）：SOL。The JAK/STAT Pathway（右上区）：抑制JAK2、STAT3表达及磷酸化（浅青色框）：GCXXD；促进JAK2、STAT3磷酸化（浅棕色）：BBR；抑制STAT3磷酸化（深紫色）：Gyp、Cur、D-Car、PI、RVSE。The NOTCH Pathway（左下区）：下调NOTCH1表达（浅蓝色框）：AT-Ⅰ、Lut、Tri、DA、β-El、XTSJ。The PI3K/AKT Pathway（右下区）：抑制mTOR磷酸化（浅绿色框）：Sal；抑制AKT磷酸化（黄色框）：DSD、JPYW、CKI；下调AKT表达（深绿色框）：QLDn、CTD、Aloin；抑制PI3K和AKT磷酸化（浅红色）：Sal、RGP、TET、Eri、ACA；上调PTEN表达（黄色框）：CTD；下调PI3K表达（白色框）：ZYHTR、QLDn、Aloin、CKI。备注：红色字：扶正类；蓝色字，化痰软坚类；紫色字，活血化瘀类；灰色字，清热解毒类；黄色字，理气和胃类；绿色字，以毒攻毒类。
图4 中医药调控胃癌NF-KB/PI3K/JAK/Notch信号通路的机制
1.6 中医药调控Wnt/β-catenin和Hedgehog信号通路 Wnt/β-catenin通路的异常激活在胃癌发展中至关重要[91]。过表达的转录因子Gli可促进胃癌侵袭。研究发现，扶正类、化痰软坚类、清热解毒类、活血化瘀类中医药可通过调控Wnt/β-catenin和Hedgehog通路来抑制胃癌进展（详见表3）[40, 68, 92-97]。
表3 调控Wnt/β-catenin和Hedgehog信号通路的中医药及有效成分
2 中医药重塑胃癌免疫微环境（TIME）
2.1 中医药调控肿瘤相关巨噬细胞（TAMs） 在胃癌中，TAMs倾向于极化为M2型，其高富集预示着胃癌预后不良。[98]。研究发现，铁皮石斛、鱼腥草、灵芝、柑橘、白术、苦豆子的有效成分：铁皮石斛多糖DOP）、棕榈酸（PA）、灵芝酮三醇（GAN）、香叶木素（DIO）、白术内酯II（AT-Ⅱ）、槐定碱（SOP）和加味健脾养正汤（mJPYZ）可通过促进TAMs向M1型极化/转化来抑制胃癌进展（详见图5）[82, 99-105]。
2.2 中医药调控自然杀伤细胞（NK细胞） 胃癌组织内的NK细胞密度是患者总体生存期的独立预后因素[106]。研究发现，石胡荽、香菇的有效成分：羽扇豆醇（LUP）、香菇多糖（LEN）和参麦注射液（SMI）、含人参中药制剂（G-TMPs）可通过增加NK细胞数量与活性来抑制胃癌进展（详见图5）[107-109]。
2.3 中医药调控树突状细胞（DC） 胃癌患者体内增加的循环浸润浆细胞样树突状细胞（pDCs）与癌症分期呈正相[110]。研究发现，黄芪（AMs）和六味地黄丸（LWDHP）可通过促进DC成熟来抑制胃癌进展（详见图5）[111, 112]。
2.4 中医药调控髓源性抑制细胞（MDSCs） MDSCs在胃癌发展过程中迅速扩增并迁移到胃癌组织中形成免疫抑制环境[113]。研究发现，姜黄的有效成分：姜黄素（Cur）和槐耳清膏正丁醇萃取物（TRMBE）、健脾养正方（JPYZ）、胃积消（WJX）、阳和汤（YHT）可通过降低MDSCs水平来抑制胃癌进展（详见图5）[114-118]。
2.5 中医药调控T细胞 在TIME中，Th1/Th2比例失衡可导致免疫逃逸[119]。Treg是胃癌患者不良结局的独立危险因素，与术后较短的生存期呈正相关[120]。Treg中高表达的Foxp3与胃癌进展呈正相关[121]。CTL在TIME中发生功能耗竭，其表面PD-1表达上调，而Toll样受体2表达下调[122, 123]。研究发现，齐墩果、黄芪、丹参的有效成分：齐墩果酸（OA）、黄芪多糖（AP）、中性多糖组分（SMPA）和黄精双参汤（HJSS）、复方苦参注射液（CKI）、补中益气汤（BZYQT）、加味补中益气汤（mBYD）可通过调节T细胞来抑制胃癌进展[79, 124-129]（详见图5）。
TAMs（黄色框）：SOP、AT-Ⅱ通过抑制PI3K磷酸化、调控TLR4通路，促进M1型极化；GAN、DIO、mJPYZ通过抑制STAT6磷酸化、抑制TRAF2/NF-κB通路、减少PKM2，阻碍M2型极化；DOP、PA、mJPYZ通过调控JAG1/NOTCH1通路、TLR4通路、降低PI3Kγ活性，促进M2型向M1型转化。Th1/Th2（蓝色框）:BZYQT、CKI通过降低IL-4水平、增加Th1，纠正Th1/Th2失衡状态。Treg（深紫色框）：OA、mBYD、AP可下调Treg/Th17、减少PD-1+Tregs、FoxP3+Tregs数量。DC（浅紫色框）：AMs、LWDHP可促进其成熟。iCD8+T（青色框）:mBYD通过PI3K/AKT通路，抑制胃癌细胞上PD-L1表达。NK细胞（粉色框）：LEN、LUP通过激活PI3K/AKT和Wnt/β-catenin通路，增强其杀伤活性；SMI、G-TMPs可显著增加其数量。MDSC（灰色框）：TRMBE、WJX、YHT可减少其数量；Cur诱导其向M1型TAMs极化；JPYZ通过重塑肠道菌群结构，增强SCFAs生成，减少其数量，进而阻碍肺转移前微环境形成。备注：红色字：扶正类；蓝色字：理气和胃类；绿色字：清热解毒；紫色字：以毒攻毒类；黄色字：活血化瘀类；青色字：化痰软坚类。
图5 中医药重塑胃癌免疫微环境的机制
3 小结与展望
本文系统综述了六种不同类药性中医药在胃癌分子治疗和免疫微环境重塑中的研究进展：在分子治疗层面，红景天苷可通过抑制mTOR磷酸化，促进胃癌细胞自噬；红参多糖可通过抑制PI3K、AKT磷酸化，诱导胃癌细胞铁死亡；在免疫微环境重塑层面，棕榈酸可通过调控TLR4通路，诱导M2型TAMs向M1型表型转化。研究显示，同类药性中医药的分子靶点调控网络既呈现一定共性，符合中医辨证论治理论，又表现出一定异质性，提示中医药多组分、多靶点的协同作用机制。值得关注的是，健脾养正方可通过调节肠道菌群，重塑脂代谢，提高机体免疫力。这种“中医药-菌群-代谢-免疫”四位一体的调控模式，为中医药在胃癌治疗领域的研究提供了创新范式。
中医药治疗胃癌的研究已取得显著进展，但尚存在若干瓶颈：①需系统开展动物实验的抗癌机制验证研究；②需构建符合中医证候特征的实验动物模型；③应基于君臣佐使组方理论，运用系统生物学及高通量筛选技术，解析中药复方多组分间的协同增效机制与毒性拮抗效应，建立最优配比数学模型；④亟需探索中药活性成分与分子靶向治疗、免疫检查点抑制剂的协同治疗方案，构建中西医联合干预的精准治疗框架；⑤针对当前临床研究存在的单中心设计、样本规模受限等问题，亟需开展多中心、大样本量的随机对照临床试验。未来，通过整合多组学技术、人工智能算法及新型药物递送技术，有望深入剖析中医药在分子、细胞及整体水平治疗胃癌的作用机制、优化配伍方案和实现有效成分的精准递送，从而推动中医药治疗胃癌策略的范式革新，显著提升其临床疗效。
参考文献
[1] SONG Z, WU Y, YANG J, et al. Progress in the treatment of advanced gastric cancer [J]. Tumour Biol, 2017, 39(7): 1010428317714626.
[2] ZENG H, CHEN W, ZHENG R, et al. Changing cancer survival in China during 2003-15: a pooled analysis of 17 population-based cancer registries [J]. Lancet Glob Health, 2018, 6(5): e555-e567.
[3] 凤元芳, 梁惠. 扶正培本祛邪汤辅助调强放疗治疗中晚期胃癌患者的临床观察 [J]. 世界中西医结合杂志, 2023, 18(09): 1847-1852.
[4] 陈晓萌, 范田. 养正消积胶囊辅助放疗治疗晚期胃癌患者的近期疗效及作用机制 [J]. 医药论坛杂志, 2022, 43(17): 5-9.
[5] 闵亮, 祁宏, 王海桥,等. 痰瘀同治方联合化疗治疗进展期胃癌术后60例临床观察 [J]. 中国中西医结合消化杂志, 2017, 25(07): 481-484.
[6] ZHANG X, YUAN Y, XI Y, et al. Cinobufacini Injection Improves the Efficacy of Chemotherapy on Advanced Stage Gastric Cancer: A Systemic Review and Meta‐Analysis [J]. Evid Based Complement Alternat Med, 2018, 2018: 7362340.
[7] 梁冰, 张振. 补中益气汤加减联合灵龟八法治疗胃癌放疗后癌性疲乏临床研究 [J]. 新中医, 2024, 56(01): 179-184.
[8] 张洁, 李建波, 李巧敏,等. 仲景方对胃癌放疗后发热退热效果及NF-κB p65蛋白的变化研究 [J]. 中华中医药学刊, 2020, 38(08): 219-221.
[9] LIU Y, CHEN L, ZHANG R, et al. Efficacy and safety of elemene combined with chemotherapy in advanced gastric cancer [J]. Medicine (Baltimore), 2020, 99(11): e19481.
[10] 覃桂珍, 王芦萍, 王淼, et al. FOLFOX方案辅助复方苦参注射液治疗胃癌疗效及不良反应系统评价 [J]. 中华肿瘤防治杂志, 2019, 26(12): 881-887.
[11] 《胃癌中西医结合诊疗指南》标准化项目组. 胃癌中西医结合诊疗指南（2023年） [J]. 中国中西医结合杂志, 2024, 44(03): 261-272.
[12] YANG L, LIU Y N, GU Y, et al. Deltonin enhances gastric carcinoma cell apoptosis and chemosensitivity to cisplatin via inhibiting PI3K/AKT/mTOR and MAPK signaling [J]. World J Gastrointest Oncol, 2023, 15(10): 1739-1755.
[13] RONG L, LI Z, LENG X, et al. Salidroside induces apoptosis and protective autophagy in human gastric cancer AGS cells through the PI3K/Akt/mTOR pathway [J]. Biomed Pharmacother, 2020, 122: 109726.
[14] GENG Y-Y, YANG S, LIU Z-H, et al. Cinnamaldehyde Regulates the Migration and Apoptosis of Gastric Cancer Cells by Inhibiting the Jak2/Stat3 Pathway [J]. Dig Dis Sci, 2024, 69(8): 2875-2882.
[15] WEI X, LIU Q, LIU L, et al. Discovery of the Natural Bibenzyl Compound Erianin in Dendrobium Inhibiting the Growth and EMT of Gastric Cancer through Downregulating the LKB1-SIK2/3-PARD3 Pathway [J]. Int J Mol Sci, 2024, 25(14): 7973.
[16] CHEN M, ZHANG R, CHEN Y, et al. Nobiletin inhibits de novo FA synthesis to alleviate gastric cancer progression by regulating endoplasmic reticulum stress [J]. Phytomedicine, 2023, 116: 154902.
[17] WANG Z, YU K, HU Y, et al. Schisantherin A induces cell apoptosis through ROS/JNK signaling pathway in human gastric cancer cells [J]. Biochemical Pharmacology, 2020, 173: 113673.
[18] ZHANG J, SUN H, JIANG K, et al. Cudraxanthone L inhibits gastric cancer by regulating the MAPK signalling and promoting FAS-mediated pathway [J]. Biomed Pharmacother, 2021, 141: 111876.
[19] CHEN X, ZHAO Y, LUO W, et al. Celastrol induces ROS-mediated apoptosis via directly targeting peroxiredoxin-2 in gastric cancer cells [J]. Theranostics, 2020, 10(22): 10290-10308.
[20] BHOSALE P B, VETRIVEL P, HA S E, et al. Iridin Induces G2/M Phase Cell Cycle Arrest and Extrinsic Apoptotic Cell Death through PI3K/AKT Signaling Pathway in AGS Gastric Cancer Cells [J]. Molecules, 2021, 26(9): 2802.
[21] PENG Z, GUAN Q, LUO J, et al. Sophoridine exerts tumor-suppressive activities via promoting ESRRG-mediated β-catenin degradation in gastric cancer [J]. BMC Cancer, 2020, 20(1): 582.
[22] XU M, REN L, FAN J, et al. Berberine inhibits gastric cancer development and progression by regulating the JAK2/STAT3 pathway and downregulating IL-6 [J]. Life Sci, 2022, 290: 120266.
[23] ZHANG C, WANG X, CAI G, et al. Targeting KPNB1 with genkwadaphnin suppresses gastric cancer progression through the Nur77-mediated signaling pathway [J]. Eur J Pharmacol, 2024, 977: 176697.
[24] WANG H, GE X, QU H, et al. Glycyrrhizic Acid Inhibits Proliferation of Gastric Cancer Cells by Inducing Cell Cycle Arrest and Apoptosis [J]. Cancer Manag Res, 2020, 12: 2853-2861.
[25] ZHENG Y, GUO C, ZHANG X, et al. Garcinol acts as an antineoplastic agent in human gastric cancer by inhibiting the PI3K/AKT signaling pathway [J]. Oncol Lett, 2020, 20(1): 667-676.
[26] REN M, ZHOU X, GU M, et al. Resveratrol synergizes with cisplatin in antineoplastic effects against AGS gastric cancer cells by inducing endoplasmic reticulum stress-mediated apoptosis and G2/M phase arrest [J]. Oncol Rep, 2020, 44(4): 1605-1615.
[27] WU L, WANG L, TIAN X, et al. Germacrone exerts anti-cancer effects on gastric cancer through induction of cell cycle arrest and promotion of apoptosis [J]. BMC Complement Med Ther, 2020, 20(1): 21.
[28] LIU J, LI S M, TANG Y J, et al. Jaceosidin induces apoptosis and inhibits migration in AGS gastric cancer cells by regulating ROS-mediated signaling pathways [J]. Redox Report, 2024, 29(1): 2313366.
[29] SUN X L, ZHANG X W, ZHAI H J, et al. Magnoflorine inhibits human gastric cancer progression by inducing autophagy, apoptosis and cell cycle arrest by JNK activation regulated by ROS [J]. Biomed Pharmacother, 2020, 125: 109118.
[30] WANG Z, TANG T, WANG S, et al. Aloin Inhibits the Proliferation and Migration of Gastric Cancer Cells by Regulating NOX2–ROS-Mediated Pro-Survival Signal Pathways [J]. Drug Des Devel Ther, 2020, 14: 145-155.
[31] LU Y Y, ZHU C Y, DING Y X, et al. Cepharanthine, a regulator of keap1-Nrf2, inhibits gastric cancer growth through oxidative stress and energy metabolism pathway [J]. Cell Death Discov, 2023, 9(1): 450.
[32] LEE H, KIM W, KANG H G, et al. Geranium thunbergii extract-induced G1 phase cell cycle arrest and apoptosis in gastric cancer cells [J]. Anim Cells Syst (Seoul), 2019, 24(1): 26-33.
[33] KIM S, VETRIVEL P, HA S, et al. Apigetrin induces extrinsic apoptosis, autophagy and G2/M phase cell cycle arrest through PI3K/AKT/mTOR pathway in AGS human gastric cancer cell [J]. J Nutr Biochem, 2020, 83: 108427.
[34] LIU J, CHEN Y, CAO Z, et al. Babao Dan inhibits the migration and invasion of gastric cancer cells by suppressing epithelial–mesenchymal transition through the TGF-β/Smad pathway [J]. J Int Med Res, 2020, 48(6): 300060520925598.
[35] CHEN W, ZHANG Y, GU X, et al. Qi Ling decoction reduces gastric cancer cell metastasis by inhibiting MMP-9 through the PI3K/Akt signaling pathway [J]. Am J Transl Res, 2021, 13(5): 4591-4602.
[36] SARKAR A, DAS S, RAHAMAN A, et al. Eugenol and capsaicin exhibit anti-metastatic activity via modulating TGF-β signaling in gastric carcinoma [J]. Food Funct, 2020, 11(10): 9020-9034.
[37] ZHANG G, LI Z, DONG J, et al. Acacetin inhibits invasion, migration and TGF-β1-induced EMT of gastric cancer cells through the PI3K/Akt/Snail pathway [J]. BMC Complement Med Ther, 2022, 22(1): 10.
[38] LI L, WANG K, LIU Z, et al. Compound Kushen injection inhibits EMT of gastric cancer cells via the PI3K/AKT pathway [J]. World J Surg Oncol, 2022, 20(1): 161.
[39] CHEN G, ZHANG H, SUN H, et al. Bufalin targeting BFAR inhibits the occurrence and metastasis of gastric cancer through PI3K/AKT/mTOR signal pathway [J]. Apoptosis, 2023, 28(9-10): 1390-1405.
[40] ZANG M, HOU J, HUANG Y, et al. Crocetin suppresses angiogenesis and metastasis through inhibiting sonic hedgehog signaling pathway in gastric cancer [J]. Biochem Biophys Res Commun, 2021, 576: 86-92.
[41] YU J R, LIU Y Y, GAO Y Y, et al. Diterpenoid tanshinones inhibit gastric cancer angiogenesis through the PI3K/Akt/mTOR signaling pathway [J]. J Ethnopharmacol, 2024, 324: 117791.
[42] LIN S, TSAI S, LEE C, et al. Berberine inhibits HIF-1alpha expression via enhanced proteolysis [J]. Mol Pharmacol, 2004, 66(3): 612-619.
[43] ZANG M, HU L, ZHANG B, et al. Luteolin suppresses angiogenesis and vasculogenic mimicry formation through inhibiting Notch1-VEGF signaling in gastric cancer [J]. Biochem Biophys Res Commun, 2017, 490(3): 913-919.
[44] ZHANG L, LIU L, ZHAN S, et al. Arsenic Trioxide Suppressed Migration and Angiogenesis by Targeting FOXO3a in Gastric Cancer Cells [J]. Int J Mol Sci, 2018, 19(12): 3739.
[45] CHEN S, ZHANG L, KIM S, et al. Arsenic sulfide inhibits cell migration and invasion of gastric cancer in vitro and in vivo [J]. Drug Des Devel Ther, 2015, 9: 5579-5590.
[46] FUJIMORI Y, INOKUCHI M, TAKAGI Y, et al. Prognostic value of RKIP and p-ERK in gastric cancer [J]. J Exp Clin Cancer Res, 2012, 31(1): 30.
[47] KALLUNKI T, DENG T, HIBI M, et al. c-Jun can recruit JNK to phosphorylate dimerization partners via specific docking interactions [J]. Cell, 1996, 87(5): 929-939.
[48] GUO X, MA N, WANG J, et al. Increased p38-MAPK is responsible for chemotherapy resistance in human gastric cancer cells [J]. BMC Cancer, 2008, 8: 375.
[49] PANDEY A, VISHNOI K, MAHATA S, et al. Berberine and Curcumin Target Survivin and STAT3 in Gastric Cancer Cells and Synergize Actions of Standard Chemotherapeutic 5-Fluorouracil [J]. Nutr Cancer, 2015, 67(8): 1293-1304.
[50] LV L, YANG N, CAO Y, et al. d-Carvone inhibits the JAK/STAT3 signaling pathway and induced the apoptotic cell death in the human gastric cancer AGS cells [J]. J Biochem Mol Toxicol, 2021, 35(5): e22746.
[51] CHOI N R, CHOI W G, ZHU A, et al. Exploring the Therapeutic Effects of Atractylodes macrocephala Koidz against Human Gastric Cancer [J]. Nutrients, 2024, 16(7): 965.
[52] LEE H S, JUNG J I, KIM K H, et al. Rhus verniciflua Stokes extract suppresses migration and invasion in human gastric adenocarcinoma AGS cells [J]. Nutr Res Pract, 2020, 14(5): 463-477.
[53] MA L, HU X, ZHANG W, et al. Weifuchun suppresses the malignancy of gastric cancer cells by targeting KPNA2 through miR-26a-5p-mediated destabilization and the deactivation of the MAPK signaling pathway [J]. J Ethnopharmacol, 2024, 334: 118538.
[54] YU L, QIN J Y, SUN C, et al. Xianglian Pill combined with 5-fluorouracil enhances antitumor activity and reduces gastrointestinal toxicity in gastric cancer by regulating the p38 MAPK/NF-κB signaling pathway [J]. J Ethnopharmacol, 2024, 326: 117988.
[55] OUYANG L, LI J, CHEN X, et al. Chinese dragon's blood ethyl acetate extract suppresses gastric cancer progression through induction of apoptosis and autophagy mediated by activation of MAPK and downregulation of the mTOR‐Beclin1 signalling cascade [J]. Phytother Res, 2022, 37(2): 689-701.
[56] LI Y, GUO Q J, CHEN R, et al. Crocin Combined with Cisplatin Regulates Proliferation, Apoptosis, and EMT of Gastric Cancer Cells via the FGFR3/MAPK/ERK Pathway In vitro and In vivo [J]. Curr Cancer Drug Targets, 2024, 24(8): 835-845.
[57] SHI X F, YU Q, WANG K B, et al. Active ingredients Isorhamnetin of Croci Srigma inhibit stomach adenocarcinomas progression by MAPK/mTOR signaling pathway [J]. Sci Rep, 2023, 13(1): 12607.
[58] YANG Y, YUAN L, DU Y, et al. Network pharmacology and in vitro experiments to investigate the anti-gastric cancer effects of paeoniflorin through the RAS/MAPK signaling pathway [J]. Discov Oncol, 2024, 15(1): 659.
[59] WAN M, GAN A, DAI J, et al. Rhein induces apoptosis of AGS and MGC803 cells by regulating the Ras/PI3K/AKT and p38/MAPK signaling pathway [J]. J Pharm Pharmacol, 2024: rgae115.
[60] ZHANG Q, WANG X, CAO S, et al. Berberine represses human gastric cancer cell growth in vitro and in vivo by inducing cytostatic autophagy via inhibition of MAPK/mTOR/p70S6K and Akt signaling pathways [J]. Biomed Pharmacother, 2020, 128: 110245.
[61] SHI J, YAO D, LIU W, et al. Highly frequent PIK3CA amplification is associated with poor prognosis in gastric cancer [J]. BMC Cancer, 2012, 12: 50.
[62] AN J Y, KIM K M, CHOI M G, et al. Prognostic role of p‐mTOR expression in cancer tissues and metastatic lymph nodes in pT2b gastric cancer [J]. Int J Cancer, 2010, 126(12): 2904-2913.
[63] WANG Y, GUAN W X, ZHOU Y, et al. Red ginseng polysaccharide promotes ferroptosis in gastric cancer cells by inhibiting PI3K/Akt pathway through down-regulation of AQP3 [J]. Cancer Biol Ther, 2024, 25(1): 2284849.
[64] XUE W, SUN R, HAO Z, et al. Tetrandrine inhibits migration and invasion of BGC‐823 and MKN‐45 cells by regulating PI3K/AKT/mTOR signaling pathway [J]. Chem Biol Drug Des, 2023, 101(4): 927-936.
[65] YU J, SONG S, JIAO J, et al. ZiYinHuaTan Recipe Inhibits Cell Proliferation and Promotes Apoptosis in Gastric Cancer by Suppressing PI3K/AKT Pathway [J]. Biomed Res Int, 2020, 2020: 2018162.
[66] PAN B, WANG Y, WU C, et al. A Mechanism of Action Study on Danggui Sini Decoction to Discover Its Therapeutic Effect on Gastric Cancer [J]. Front Pharmacol, 2021, 11: 592903.
[67] TANG H, HUANG W, YANG Q, et al. Jianpi Yangwei decoction promotes apoptosis and suppresses proliferation of 5-fluorouracil resistant gastric cancer cells in vitro and in vivo [J]. BMC Complement Med Ther, 2020, 20(1): 337.
[68] LIU Z, WANG Z, LIU X, et al. Scutellarin Suppressed Proliferation and Induced Apoptosis in Gastric Cancer via Wnt/β-catenin Signaling Pathway [J]. Curr Pharm Des, 2023, 29(5): 368-378.
[69] SONG M, WANG X, LUO Y, et al. Cantharidin suppresses gastric cancer cell migration/invasion by inhibiting the PI3K/Akt signaling pathway via CCAT1 [J]. Chem Biol Interact, 2020, 317: 108939.
[70] SHAN H, ZHANG X, MI Y, et al. Eriodictyol Suppresses Gastric Cancer Cells via Inhibition of PI3K/AKT Pathway [J]. Pharmaceuticals (Basel), 2022, 15(12).
[71] GAO J, YANG S, XIE G, et al. Integrating Network Pharmacology and Experimental Verification to Explore the Pharmacological Mechanisms of Aloin Against Gastric Cancer [J]. Drug Des Devel Ther, 2022, 16: 1947-1961.
[72] WU H, LAI W, WANG Q, et al. Gypenoside induces apoptosis by inhibiting the PI3K/AKT/mTOR pathway and enhances T-cell antitumor immunity by inhibiting PD-L1 in gastric cancer [J]. Front Pharmacol, 2024, 15: 1243353.
[73] YANG Y, YUAN L, MENG F, et al. Gancao Xiexin Decoction inhibits gastric carcinoma proliferation and migration by regulating the JAK2/STAT3 signalling pathway [J]. J Ethnopharmacol, 2024, 319(Pt2): 117241.
[74] HAM I H, WANG L, LEE D, et al. Curcumin inhibits the cancer‑associated fibroblast‑derived chemoresistance of gastric cancer through the suppression of the JAK/STAT3 signaling pathway [J]. Int J Oncol, 2022, 61(1): 85.
[75] HAN J, KAN J, WANG X, et al. Polyphyllin I suppresses proliferation and promotes apoptosis of gastric cancer cell by inhibiting stat3 phosphorylation [J]. Transl Cancer Res, 2020, 9(8): 4715-4725.
[76] BORGHI A, VERSTREPEN L, BEYAERT R. TRAF2 multitasking in TNF receptor-induced signaling to NF-kappaB, MAP kinases and cell death [J]. Biochem Pharmacol, 2016, 116: 1-10.
[77] MA X, KONG L, ZHU W, et al. Curcumol Undermines SDF-1α/CXCR4/NF-κB Signaling Pathway to Suppress the Progression of Chronic Atrophic Gastritis (CAG) and Gastric Cancer [J]. Evid Based Complement Alternat Med, 2022, 2022: 3219001.
[78] ABUDUROUSULI K, TALIHATI Z, HAILATI S, et al. Investigation of target genes and potential mechanisms related to compound Xiao-ai-fei honey ointment based on network pharmacology and bioinformatics analysis [J]. Medicine (Baltimore), 2023, 102(32): e34629.
[79] XU R, WU J, ZHANG X, et al. Modified Bu-zhong-yi-qi decoction synergies with 5 fluorouracile to inhibits gastric cancer progress via PD-1/PD- L1-dependent T cell immunization [J]. Pharmacol Res, 2020, 152: 104623.
[80] LI J, DAI C, SHEN L. Ursolic Acid Inhibits Epithelial-Mesenchymal Transition through the Axl/NF-κB Pathway in Gastric Cancer Cells [J]. Evid Based Complement Alternat Med, 2019, 2019: 2474805.
[81] SU K, YAO X, GUO C, et al. Solasodine suppresses the metastasis of gastric cancer through claudin-2 via the AMPK/STAT3/NF-κB pathway [J]. Chem Biol Interact, 2023, 379: 110520.
[82] ZHANG F, LUO H. Diosmetin inhibits the growth and invasion of gastric cancer by interfering with M2 phenotype macrophage polarization [J]. J Biochem Mol Toxicol, 2023, 37(10): e23431.
[83] CHEN H, JIANG T, CHEN H, et al. Brusatol reverses lipopolysaccharide-induced epithelial-mesenchymal transformation and induces apoptosis through PI3K/Akt/NF-кB pathway in human gastric cancer SGC-7901 cells [J]. Anticancer Drugs, 2020, 32(4): 394-404.
[84] WU X, LIU W, TANG D, et al. Prognostic values of four Notch receptor mRNA expression in gastric cancer [J]. Sci Rep, 2016, 6: 28044.
[85] MA L, MAO R, SHEN K, et al. Atractylenolide I-mediated Notch pathway inhibition attenuates gastric cancer stem cell traits [J]. Biochem Biophys Res Commun, 2014, 450(1): 353-359.
[86] ZANG M-D, HU L, FAN Z-Y, et al. Luteolin suppresses gastric cancer progression by reversing epithelial-mesenchymal transition via suppression of the Notch signaling pathway [J]. J Transl Med, 2017, 15(1): 52.
[87] XIANG S, ZHAO Z, ZHANG T, et al. Triptonide effectively suppresses gastric tumor growth and metastasis through inhibition of the oncogenic Notch1 and NF-κB signaling pathways [J]. Toxicol Appl Pharmacol, 2020, 388: 114870.
[88] ZHEN JUN S, YUAN YUAN Z, YING YING F, et al. β,β-Dimethylacrylshikonin exerts antitumor activity via Notch-1 signaling pathway in vitro and in vivo [J]. Biochem Pharmacol, 2012, 84(4): 507-512.
[89] YAN B, ZHOU Y, FENG S, et al. β-Elemene-Attenuated Tumor Angiogenesis by Targeting Notch-1 in Gastric Cancer Stem-Like Cells [J]. Evid Based Complement Alternat Med, 2013, 2013: 268468.
[90] YAN B, LIU L, ZHAO Y, et al. Xiaotan Sanjie decoction attenuates tumor angiogenesis by manipulating Notch-1-regulated proliferation of gastric cancer stem-like cells [J]. World J Gastroenterol, 2014, 20(36): 13105-13118.
[91] HUA Y, YANG Y, LI Q, et al. Oligomerization of Frizzled and LRP5/6 protein initiates intracellular signaling for the canonical WNT/β-catenin pathway [J]. J Biol Chem, 2018, 293(51): 19710-19724.
[92] CHEN X, YUE W, TIAN L, et al. A plant-based medicinal food inhibits the growth of human gastric carcinoma by reversing epithelial–mesenchymal transition via the canonical Wnt/β-catenin signaling pathway [J]. BMC Complement Med Ther, 2021, 21(1): 137.
[93] ZHOU H, HU X, LI N, et al. Loganetin and 5‐fluorouracil synergistically inhibit the carcinogenesis of gastric cancer cells via down‐regulation of the Wnt/β‐catenin pathway [J]. J Cell Mol Med, 2020, 24(23): 13715-13726.
[94] ZHANG T, LIU G Y, CAO J L, et al. Peimine‐induced apoptosis and inhibition of migration by regulating reactive oxygen species‐mediated MAPK/STAT3/NF‐κB and Wnt/β‐catenin signaling pathways in gastric cancer MKN‐45 cells [J]. Drug Dev Res, 2022, 83(7): 1683-1696.
[95] YE C, YAO Z, WANG Y, et al. Asiaticoside promoted ferroptosis and suppressed immune escape in gastric cancer cells by downregulating the Wnt/β-catenin pathway [J]. Int Immunopharmacol, 2024, 134: 112175.
[96] XU Q H, XIAO Y, LI X Q, et al. Resveratrol Counteracts Hypoxia-Induced Gastric Cancer Invasion and EMT through Hedgehog Pathway Suppression [J]. Anticancer Agents Med Chem, 2020, 20(9): 1105-1114.
[97] ZHANG X, ZHANG C, REN Z, et al. Curcumin Affects Gastric Cancer Cell Migration, Invasion and Cytoskeletal Remodeling Through Gli1-β-Catenin [J]. Cancer Manag Res, 2020, 12: 3795-3806.
[98] LIU J, PENG C, YANG G, et al. Distribution pattern of tumor associated macrophages predicts the prognosis of gastric cancer [J]. Oncotarget, 2017, 8(54): 92757-69.
[99] ZHAO Y, LU X, HUANG H, et al. Dendrobium officinale polysaccharide Converts M2 into M1 Subtype Macrophage Polarization via the STAT6/PPAR-r and JAGGED1/NOTCH1 Signaling Pathways to Inhibit Gastric Cancer [J]. Molecules, 2023, 28(20): 7062.
[100] ZHANG Y, LI J, LI F, et al. Palmitic acid combined with γ-interferon inhibits gastric cancer progression by modulating tumor-associated macrophages’ polarization via the TLR4 pathway [J]. J Cancer Res Clin Oncol, 2023, 149(10): 7053-7067.
[101] ZHANG L, SHI P, JIN P, et al. Ganodermanontriol regulates tumor-associated M2 macrophage polarization in gastric cancer [J]. Aging (Albany NY), 2024, 16(2): 1390-1398.
[102] 袁梦云, 张星星, 谢晓东,等. 基于巨噬细胞极化观察白术内酯Ⅱ对胃癌细胞的作用 [J]. 中国实验方剂学杂志, 2020, 26(21): 100-8.
[103] ZHUANG H, DAI X, ZHANG X, et al. Sophoridine suppresses macrophage-mediated immunosuppression through TLR4/IRF3 pathway and subsequently upregulates CD8+ T cytotoxic function against gastric cancer [J]. Biomed Pharmacother, 2020, 121: 109636.
[104] WU J, YUAN M, SHEN J, et al. Effect of modified Jianpi Yangzheng on regulating content of PKM2 in gastric cancer cells-derived exosomes [J]. Phytomedicine, 2022, 103: 154229.
[105] YUAN M, ZOU X, LIU S, et al. Modified Jian-pi-yang-zheng decoction inhibits gastric cancer progression via the macrophage immune checkpoint PI3Kγ [J]. Biomed Pharmacother, 2020, 129: 110440.
[106] LI T, ZHANG Q, JIANG Y, et al. Gastric cancer cells inhibit natural killer cell proliferation and induce apoptosis via prostaglandin E2 [J]. OncoImmunology, 2015, 5(2): e1069936.
[107] INA K, KATAOKA T, ANDO T. The use of lentinan for treating gastric cancer [J]. Anticancer Agents Med Chem, 2013, 13(5): 681-688.
[108] WU X, LIU J, LU X, et al. The enhanced effect of lupeol on the destruction of gastric cancer cells by NK cells [J]. Int Immunopharmacol, 2013, 16(2): 332-340.
[109] 林胜友, 刘鲁明, 吴良村,等. 参麦注射液对胃癌化疗后免疫功能影响的观察 [J]. 中国中西医结合杂志, 1995, (08): 451-453.
[110] LIU W, ZHAO J, LI Q, et al. Gastric cancer patients have elevated plasmacytoid and CD1c+ dendritic cells in the peripheral blood [J]. Oncol Lett, 2018, 15(4): 5087-5092.
[111] TIAN Y, LI X, LI H, et al. Astragalus mongholicus regulate the Toll-like-receptor 4 meditated signal transduction of dendritic cells to restrain stomach cancer cells [J]. Afr J Tradit Complement Altern Med, 2014, 11(3): 92-96.
[112] 孙小艳, 于波, 林黎娟. 六味地黄丸联合树突状细胞对胃癌细胞的抑制作用 [J]. 中国当代医药, 2020, 27(32): 4-7+253.
[113] GABRILOVICH D I, NAGARAJ S. Myeloid-derived suppressor cells as regulators of the immune system [J]. Nature Reviews Immunology, 2009, 9(3): 162-74.
[114] TU S, JIN H, SHI J, et al. Curcumin Induces the Differentiation of Myeloid-Derived Suppressor Cells and Inhibits Their Interaction with Cancer Cells and Related Tumor Growth [J]. Cancer Prev Res (Phila), 2012, 5(2): 205-215.
[115] XU J, YUAN L, HU C, et al. Trametes robiniophila Murr Sensitizes Gastric Cancer Cells to 5-Fluorouracil by Modulating Tumor Microenvironment [J]. Front Pharmacol, 2022, 13: 911663.
[116] ZHU X, ZHANG X, SHEN J, et al. Gut microbiota-dependent modulation of pre-metastatic niches by Jianpi Yangzheng decoction in the prevention of lung metastasis of gastric cancer [J]. Phytomedicine, 2024, 128: 155413.
[117] 钟祥寿, 沈贵洲, 秦惠河,等. 胃积消联合化疗治疗晚期胃癌疗效及对MDSCs、Treg细胞和免疫因子的影响 [J]. 现代中西医结合杂志, 2021, 30(09): 974-978.
[118] 田同德, 杨峰, 岳立云, 等. 阳和汤对晚期胃癌阳虚证患者的化疗增效及其对肿瘤炎症因子,Treg,MDSCs水平的影响 [J]. 中国实验方剂学杂志, 2016, 22(22): 160-164.
[119] OKITA Y, OHIRA M, TANAKA H, et al. Alteration of CD4 T cell subsets in metastatic lymph nodes of human gastric cancer [J]. Oncol Rep, 2015, 34(2): 639-647.
[120] 郭天威, 张闽, 刘志菊,等. 胃癌组织中FOXP3在不同部位表达与临床病理特征及预后的相关性 [J]. 临床与实验病理学杂志, 2020, 36(08): 893-898.
[121] FEI Y, CAO Y, GU Y, et al. Intratumoral Foxp3+RORγt+ T cell infiltration determines poor prognosis and immunoevasive contexture in gastric cancer patients [J]. Cancer Immunol Immunother, 2022 71(1): 1-11.
[122] OYA Y, HAYAKAWA Y, KOIKE K. Tumor microenvironment in gastric cancers [J]. Cancer Sci, 2020, 111(8): 2696-2707.
[123] XU J, GUO R, JIA J, et al. Activation of Toll-like receptor 2 enhances peripheral and tumor-infiltrating CD8+ T cell cytotoxicity in patients with gastric cancer [J]. BMC Immunol, 2021, 22(1): 67.
[124] WANG N, YANG J, LU J, et al. A polysaccharide from Salvia miltiorrhiza Bunge improves immune function in gastric cancer rats [J]. Carbohydr Polym, 2014, 111: 47-55.
[125] YANG C, XU X, WU M, et al. Huang-Jin-Shuang-Shen Decoction promotes CD8+ T-cell-mediated anti-tumor immunity by regulating chemokine CXCL10 in gastric cancer [J]. Phytomedicine, 2024, 135: 156065.
[126] 葛锐, 袁艳. 复方苦参注射液对胃癌化疗患者Th1/Th2细胞漂移和骨髓抑制的影响 [J]. 河北医药, 2019, 41(13): 1970-1973.
[127] 裴俊文, 孙太振, 付槟梵,等. 补中益气汤加减对胃癌患者Th1、Th2细胞因子及Th1/Th2免疫平衡的影响 [J]. 中华中医药杂志, 2020, 35(06): 3160-3163.
[128] XU Q, PENG H, LU X, et al. Oleanolic acid regulates the Treg/Th17 imbalance in gastric cancer by targeting IL-6 with miR-98-5p [J]. Cytokine, 2021, 148.
[129] 吕彩霞, 苑晓烨, 邵伟华,等. 黄芪多糖对老年晚期胃癌病人外周血中调节性T细胞的影响 [J]. 实用老年医学, 2021, 35(06): 564-567.
