| 166 | 0 | 10 |
| 下载次数 | 被引频次 | 阅读次数 |
胃癌患者死亡的主要原因是癌细胞的转移，系统化疗、放疗、手术、免疫治疗和靶向治疗都是胃癌治疗的重要组成部分，由于胃癌早期不容易被发现，因此我国胃癌患者具有分期晚、肿瘤负荷大等特点。对于晚期胃癌手术治愈率低，且放化疗疗效欠佳，中医药以其特有的辨证论治方式，在增强免疫力多靶点多途径对抗肿瘤的同时还具有减毒增效的功能，众多研究表明肿瘤微环境是导致胃癌进展的重要因素，在胃癌肿瘤中心、浸润前沿以及肿瘤间质中存在大量的肿瘤相关巨噬细胞(tumor-associated macrophages, TAMs),在促进肿瘤侵袭和转移中至关重要。中药提取物和复方具有调控TAMs抑制胃癌细胞侵袭和转移，抑制血管生成，提高免疫及治疗化疗耐药的功能，从而起到干预胃癌的作用。因此，总结TAMs调控胃癌的机制及中药干预TAMs的研究进展，对于改善胃癌患者的临床症状和新药研发具有重要意义。
Abstract：The main reason for death of patients with gastric cancer is metastasis of cancer cells. Systematic chemotherapy, radiotherapy, surgery, immunotherapy and targeted therapy are all important components of the treatment of gastric cancer. As it is not easy to be found in early stage, patients with gastric cancer in our country have the characteristics of late staging and large tumor load. For advanced gastric cancer, the cure rate of surgery is low and the curative effect of radiotherapy and chemotherapy is poor. Traditional Chinese medicine, with its unique syndrome differentiation method, can enhance immunity and fight against tumors by multiple targets and multiple approaches, and at the same time, it also has the function of decreasing toxicity and increasing efficiency. Numerous studies have shown that tumor microenvironment is an important factor leading to the progression of gastric cancer. There are a large number of tumor-associated macrophages(TAMs) in the tumor center, invasive front and tumor stroma of gastric cancer, which play an important role in promoting tumor invasion and metastasis. Chinese herbal extracts and compounds can regulate TAMs to inhibit the invasion and metastasis of gastric cancer cells, inhibit angiogenesis, improve immunity and treat chemotherapy resistance, and thus play a role in the intervention of gastric cancer. Therefore, it is of great significance to summarize the mechanism of TAMs regulating gastric cancer and the research progress of traditional Chinese medicine intervention in TAMs for improving the clinical symptoms of gastric cancer patients and the development of new drugs.
[1] Wang Z,Han W,Xue F,et al.Nationwide gastric cancer prevention in China,2021-2035:a decision analysis on effect,affordability and cost-effectiveness optimisation [J].Gut,2022,71(12):2391-2400.
[2] Guan W L,He Y,Xu R H.Gastric cancer treatment:recent progress and future perspectives [J].J Hematol Oncol,2023,16(1):57.
[3] Pan Y,Yu Y,Wang X,et al.Tumor-associated macrophages in tumor immunity [J].Front Immunol,2020,11:583084.
[4] Toledo B,Chen L Z,Paniagua-Sancho M,et al.Deciphering the performance of macrophages in tumour microenvironment:a call for precision immunotherapy [J].J Hematol Oncol,2024,17(1):44.
[5] Luo H,Vong C T,Chen H,et al.Naturally occurring anti-cancer compounds:shining from Chinese herbal medicine [J].Chin Med,2019,14:48.
[6] Zhang G,Gao Z,Guo X,et al.CAP2 promotes gastric cancer metastasis by mediating the interaction between tumor cells and tumor-associated macrophages [J].J Clin Invest,2023,133(21):e166224.
[7] Yang F,Nam S,Zhao R,et al.A novel synthetic derivative of the natural product berbamine inhibits cell viability and induces apoptosis of human osteosarcoma cells,associated with activation of JNK/AP-1 signaling [J].Cancer Biol Ther,2013,14(11):1024-1031.
[8] Gambardella V,Castillo J,Tarazona N,et al.The role of tumor-associated macrophages in gastric cancer development and their potential as a therapeutic target [J].Cancer Treat Rev,2020,86:102015.
[9] Quail D F,Joyce J A.Microenvironmental regulation of tumor progression and metastasis [J].Nat Med,2013,19(11):1423-1437.
[10] Yan D,Wang H W,Bowman R L,et al.STAT3 and STAT6 signaling pathways synergize to promote cathepsin secretion from macrophages via IRE1α activation [J].Cell Rep,2016,16(11):2914-2927.
[11] Lee S,Lee E,Ko E,et al.Tumor-associated macrophages secrete CCL2 and induce the invasive phenotype of human breast epithelial cells through upregulation of ERO1-α and MMP-9 [J].Cancer Lett,2018,437:25-34.
[12] Costa-Silva B,Aiello N M,Ocean A J,et al.Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver [J].Nat Cell Biol,2015,17(6):816-826.
[13] Zheng P,Luo Q,Wang W,et al.Tumor-associated macrophages-derived exosomes promote the migration of gastric cancer cells by transfer of functional Apolipoprotein E [J].Cell Death Dis,2018,9(4):434.
[14] Chen Y C,Pohl G,Wang T L,et al.Apolipoprotein E is required for cell proliferation and survival in ovarian cancer [J].Cancer Res,2005,65(1):331-337.
[15] Piao H,Fu L,Wang Y,et al.A positive feedback loop between gastric cancer cells and tumor-associated macrophage induces malignancy progression [J].J Exp Clin Cancer Res,2022,41(1):174.
[16] Javle M,Smyth E C,Chau I.Ramucirumab:successfully targeting angiogenesis in gastric cancer [J].Clin Cancer Res,2014,20(23):5875-5881.
[17] Shen Z,Yan Y,Ye C,et al.The effect of Vasohibin-1 expression and tumor-associated macrophages on the angiogenesis in vitro and in vivo [J].Tumour Biol,2016,37(6):7267-7276.
[18] Kawahara A,Hattori S,Akiba J,et al.Infiltration of thymidine phosphorylase-positive macrophages is closely associated with tumor angiogenesis and survival in intestinal type gastric cancer [J].Oncol Rep,2010,24(2):405-415.
[19] Park J Y,Sung J Y,Lee J,et al.Polarized CD163+ tumor-associated macrophages are associated with increased angiogenesis and CXCL12 expression in gastric cancer [J].Clin Res Hepatol Gastroenterol,2016,40(3):357-365.
[20] Oshima H,Popivanova B K,Oguma K,et al.Activation of epidermal growth factor receptor signaling by the prostaglandin E(2) receptor EP4 pathway during gastric tumorigenesis [J].Cancer Sci,2011,102(4):713-719.
[21] Yuan Y,Wu D,Hou Y,et al.Wnt signaling:modulating tumor-associated macrophages and related immunotherapeutic insights [J].Biochem Pharmacol,2024,223:116154.
[22] Wang Y,Shang K,Zhang N,et al.Tumor-associated macrophage-derived exosomes promote the progression of gastric cancer by regulating the P38MAPK signaling pathway and the immune checkpoint PD-L1 [J].Cancer Biother Radiopharm,2021.
[23] Sharma P,Siddiqui B A,Anandhan S,et al.The next decade of immune checkpoint therapy [J].Cancer Discov,2021,11(4):838-857.
[24] Shi T,Zhang Y,Wang Y,et al.DKK1 promotes tumor immune evasion and impedes anti-PD-1 treatment by inducing immunosuppressive macrophages in gastric cancer [J].Cancer Immunol Res,2022,10(12):1506-1524.
[25] Lin C,He H,Liu H,et al.Tumour-associated macrophages-derived CXCL8 determines immune evasion through autonomous PD-L1 expression in gastric cancer [J].Gut,2019,68(10):1764-1773.
[26] Zhang H,Li R,Cao Y,et al.Poor clinical outcomes and immunoevasive contexture in intratumoral IL-10-producing macrophages enriched gastric cancer patients [J].Ann Surg,2022,275(4):e626-e635.
[27] Zhou Y,Chen Y,Shi Y,et al.FAM117B promotes gastric cancer growth and drug resistance by targeting the KEAP1/NRF2 signaling pathway [J].J Clin Invest,2023,133(3):e158705.
[28] Hu X,Ma Z,Xu B,et al.Glutamine metabolic microenvironment drives M2 macrophage polarization to mediate trastuzumab resistance in HER2-positive gastric cancer [J].Cancer Commun,2023,43(8):909-937.
[29] Su P,Jiang L,Zhang Y,et al.Crosstalk between tumor-associated macrophages and tumor cells promotes chemoresistance via CXCL5/PI3K/AKT/mTOR pathway in gastric cancer [J].Cancer Cell Int,2022,22(1):290.
[30] Yu S,Li Q,Yu Y,et al.Activated HIF1α of tumor cells promotes chemoresistance development via recruiting GDF15-producing tumor-associated macrophages in gastric cancer [J].Cancer Immunol Immunother,2020,69(10):1973-1987.
[31] Ngabire D,Niyonizigiye I,Patil M P,et al.M2 macrophages mediate the resistance of gastric adenocarcinoma cells to 5-fluorouracil through the expression of integrin β 3,focal adhesion kinase,and cofilin [J].J Immunol Res,2020,2020:1731457.
[32] Yu S,Li Q,Wang Y,et al.Tumor-derived LIF promotes chemoresistance via activating tumor-associated macrophages in gastric cancers [J].Exp Cell Res,2021,406(1):112734.
[33] Yu D,Chang Z,Liu X,et al.Macrophage-derived exosomes regulate gastric cancer cell oxaliplatin resistance by wrapping circ 0008253 [J].Cell Cycle,2023,22(6):705-717.
[34] Zheng P,Chen L,Yuan X,et al.Exosomal transfer of tumor-associated macrophage-derived miR-21 confers cisplatin resistance in gastric cancer cells [J].J Exp Clin Cancer Res,2017,36(1):53.
[35] Qu B,Liu J,Peng Z,et al.Macrophages enhance cisplatin resistance in gastric cancer through the transfer of circTEX2 [J].J Cell Mol Med,2024,28(5):e18070.
[36] Fu Q,Wu X,Lu Z,et al.TMEM205 induces TAM/M2 polarization to promote cisplatin resistance in gastric cancer [J].Gastric Cancer,2024,27(5):998-1015.
[37] Zhu L,Huang Y,Li H,et al.Helicobacter pylori promotes gastric cancer progression through the tumor microenvironment [J].Appl Microbiol Biotechnol,2022,106(12):4375-4385.
[38] Deng R,Zheng H,Cai H,et al.Effects of helicobacter pylori on tumor microenvironment and immunotherapy responses [J].Front Immunol,2022,13:923477.
[39] Yu B,de Vos D,Guo X,et al.IL-6 facilitates cross-talk between epithelial cells and tumor-associated macrophages in Helicobacter pylori-linked gastric carcinogenesis [J].Neoplasia,2024,50:100981.
[40] Che Y,Geng B,Xu Y,et al.Helicobacter pylori-induced exosomal MET educates tumour-associated macrophages to promote gastric cancer progression [J].J Cell Mol Med,2018,22(11):5708-5719.
[41] 赵璐，许佳豪，张玲.人参皂苷抗肿瘤作用机制的研究进展[J].中国现代应用药学，2023,40(14):2016-2022.Zhao L,Xu J H,Zhang L.Research progress on the anti-tumor mechanism of ginsenosides [J].Chin J Mod Appl Pharm,2023,40(14):2016-2022.
[42] 杨静，付裕刚，刁海彦，等.人参皂苷通过抑制肿瘤相关巨噬细胞M2极化对HepG2细胞增殖凋亡的影响[J].中华中医药学刊，2025,43(6):230-234,293.Yang J,Fu Y G,Diao H Y,et al.Effect of total ginsenoside on HepG2 cell proliferation and apoptosis via inhibiting M2 polarization of tumor-associated macrophages [J].Chinese Archives of Traditional Chinese Medicine,2025,43(6):230-234,293.
[43] Zhang Y 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.
[44] 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.
[45] 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.
[46] 李怀玉，陈云，胡子毅，等.桦木酸在胃肠道癌症中的作用机制[J].南昌大学学报(医学版),2022,62(2):87-93.Li H Y,Chen Y,Hu Z Y,et al.Mechanism of betulinic acid in gastrointestinal cancers [J].Journal of Nanchang University (Medical Sciences),2022,62(2):87-93.
[47] Chen J L,Tai Y S,Tsai H Y,et al.Betulinic acid inhibits the stemness of gastric cancer cells by regulating the GRP78-TGF-β1 signaling pathway and macrophage polarization [J].Molecules,2023,28(4):1725.
[48] Radharani N N V,Yadav A S,Nimma R,et al.Tumor-associated macrophage derived IL-6 enriches cancer stem cell population and promotes breast tumor progression via Stat-3 pathway [J].Cancer Cell Int,2022,22(1):122.
[49] Sougiannis A T,VanderVeen B,Chatzistamou I,et al.Emodin reduces tumor burden by diminishing M2-like macrophages in colorectal cancer [J].Am J Physiol Gastrointest Liver Physiol,2022,322(3):G383-G395.
[50] 孙启棣.薯蓣皂苷调控Cx43诱导肿瘤相关巨噬细胞由M2型向M1型转化作用及机制[D].扬州：扬州大学，2022.Sun Q D.Dioscin induced tumor-associated-macrophages from M2 type to M1 type and its mechanism via Cx43 [D].Yangzhou:Yangzhou Univercity,2022.
[51] Liu C P,Zhang X,Tan Q L,et al.NF-κB pathways are involved in M1 polarization of RAW 264.7 macrophage by Polyporus polysaccharide in the tumor microenvironment [J].PLoS One,2017,12(11):e0188317.
[52] Jiang Y X,Chen Y,Yang Y,et al.Screening five qi-tonifying herbs on M2 phenotype macrophages [J].Evid Based Complement Alternat Med,2019,2019:9549315.
[53] He J,Yin P,Xu K.Effect and molecular mechanisms of traditional Chinese medicine on tumor targeting tumor-associated macrophages [J].Drug Des Devel Ther,2020,14:907-919.
[54] 易志荣.莪连颗粒通过抑制肿瘤相关巨噬细胞M2型极化及NF-κB信号通路治疗胃癌前病变的机制研究[D].南宁：广西医科大学，2022.
[55] 孙庆敏，张星星，谢晓东，等.健脾养正方调控肿瘤相关巨噬细胞极化促进胃癌细胞凋亡的机制[J].中华中医药杂志，2022,37(2):719-724.Sun Q M,Zhang X X,Xie X D,et al.Mechanism of Jianpi Yangzheng Formula regulating polarization of tumor associated macrophages and promoting apoptosis of gastric cancer cells [J].CJTCMP,2022,37(2):719-724.
[56] 陈敏.健脾养正消癥方调控肿瘤相关巨噬细胞极化抑制胃癌上皮间质转化的机制研究[D].南京：南京中医药大学，2016.
[57] 李明，郑志昌，杨继红，等.扶正解毒方治疗对小鼠前胃癌所诱导肿瘤相关巨噬细胞的影响[C]//中国中药杂志2015/专集：基层医疗机构从业人员科技论文写作培训会议论文集.2016:2110,2112.
基本信息:
DOI：
中图分类号:R273
引用信息:
[1]李若南,赵政,丁琴艳,等.肿瘤相关巨噬细胞在胃癌中的调控机制及中医药干预研究进展[J].胃肠病学和肝病学杂志,2025,34(09):1348-1354.
基金信息:
黑龙江中医药大学“双一流”中西医结合学科发展助力基金(HLJSYL21002)