CHINESE JOURNAL OF MEDICINAL GUIDE >
Research Progress on the Anti-Gastric Cancer Effects and Mechanisms of Astragaloside IV
Received date: 2025-11-14
Revised date: 2026-01-03
Accepted date: 2026-06-26
Online published: 2026-06-29
The high mortality rate of gastric cancer （GC）， chemoresistance and significant toxic side effects associated with current therapies for GC necessitate the search for low-toxicity and highly effective adjuvant treatment strategies. As the key active ingredient of the traditional Chinese medicine Astragalus membranaceus， Astragaloside IV （AS-IV） possesses extensive pharmacological properties. Characterized by its low toxicity， multi-target action， and cost-effectiveness， AS-IV has emerged as a promising candidate for the comprehensive treatment of GC. This article systematically reviews the mechanisms of action and research progress regarding AS-IV intervention throughout the entire pathological course of GC. Current evidence indicates that AS-IV can exert multi-dimensional intervention effects on the entire course of GC. In the initiation stage， it hinders the inflammation-cancer transition， protects the gastric mucosal barrier， and reverses precancerous lesions. In advanced GC， AS-IV induces tumor cell apoptosis by regulating multiple key signaling pathways while concurrently inhibiting tumor invasion and metastasis. Regarding the tumor microenvironment （TME）， it targets and remodels interstitial cell functions， alleviates the immunosuppressive state， and suppresses tumor angiogenesis. Furthermore， AS-IV enhances the sensitivity of GC cells to clinically common chemotherapeutic agents and reverses drug resistance， thereby exerting synergistic efficacy and reducing toxicity. Despite the significant potential of AS-IV in GC intervention， current research is largely confined to cell and animal experiments. Limitations such as low bioavailability and the lack of systematic elucidation of its mechanisms hinder its clinical translation. Future studies should deepen the investigation utilizing advanced experimental models， novel formulation technologies， and multi-omics approaches to facilitate the transition from bench to bedside and provide scientific basis for the potential incorporation of AS-IV into standardized GC treatment regimens.
Yuqin Wang
,
Dengqin Song
,
Dong Zhou
,
Hongci chen
,
Xiong Zhang
,
Meng Zhang
.
Research Progress on the Anti-Gastric
Cancer Effects and Mechanisms of Astragaloside IV
［1］ Bray F， Laversanne M， Sung H， et al. Global cancer statistics 2022： GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］.CA Cancer J Clin， 2024，74（3）：229-263.
［2］ Sundar R， Nakayama I， Markar SR， et al. Gastric cancer［J］.Lancet， 2025，405（10494）：2087-2102.
［3］ Cappell KM， Kochenderfer JN. Long-term outcomes following CAR T cell therapy： what we know so far［J］.Nat Rev Clin Oncol， 2023，20（6）：359-371.
［4］ Chen Bo， Dong Xinqian， Zhang Jinling， et al. Effects of oxidative stress regulation in inflammation-associated gastric cancer progression treated using traditional Chinese medicines： a review［J］.Medicine （Baltimore）， 2023，102（46）：e36157.
［5］ Lu Cuncun， Ke Lixin， Li Jieyun， et al. Chinese medicine as an adjunctive treatment for gastric cancer： methodological investigation of meta-analyses and evidence map［J］.Front Pharmacol， 2021，12：797753.
［6］ Chen Tianqi， Yang Peiying， Jia Yingjie. Molecular mechanisms of astragaloside‑IV in cancer therapy （Review）［J］.Int J Mol Med， 2021，47（3）：13.
［7］ Liang Yutong， Chen Biqiong， Liang Di， et al. Pharmacological effects of astragaloside IV： a review［J］.Molecules， 2023，28（16）：6118.
［8］ Min Liang， Wang Haiqiao， Qi Hong. Astragaloside IV inhibits the progression of liver cancer by modulating macrophage polarization through the TLR4/NF-κB/STAT3 signaling pathway［J］.Am J Transl Res， 2022，14（3）：1551-1566.
［9］ Zhou Liangxing， Li Mengpeng， Chai Zhengbin， et al. Anticancer effects and mechanisms of astragaloside‑IV （Review）［J］.Oncol Rep， 2023，49（1）：5.
［10］ Correa P. Human gastric carcinogenesis： a multistep and multifactorial process--First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention［J］.Cancer Res， 1992，52（24）：6735-6740.
［11］ Morana O， Wood W， Gregory CD. The apoptosis paradox in cancer［J］.Int J Mol Sci， 2022，23（3）：1328.
［12］ Singh P， Lim B. Targeting apoptosis in cancer［J］.Curr Oncol Rep， 2022，24（3）：273-284.
［13］ Qian Shanna， Wei Zhong， Yang Wanting， et al. The role of BCL-2 family proteins in regulating apoptosis and cancer therapy［J］.Front Oncol， 2022，12：985363.
［14］ Cai Tiantian， Zhang Chengzhe， Zhao Ziming， et al. The gastric mucosal protective effects of astragaloside IV in mnng-induced GPL rats［J］.Biomed Pharmacother， 2018，104：291-299.
［15］ Wang Zhengguang， Dong Liuyi， Zhen Yinan， et al. Astragalus extract inhibits proliferation but enhances apoptosis in gastric cancer［J］.Pak J Pharm Sci， 2016，29（5）：1473-1482.
［16］ 郭英.黄芪甲苷通过抑制AKT和NF-κB通路诱导胃癌MGC-803细胞凋亡［J］.国际检验医学杂志，2018，39（19）：2341-2344.
［17］ Li Fagen， Cao Ke， Wang Maoyun， et al. Astragaloside IV exhibits anti-tumor function in gastric cancer via targeting circRNA dihydrolipoamide S-succinyltransferase （circDLST）/miR-489-3p/ eukaryotic translation initiation factor 4A1（EIF4A1） pathway［J］.Bioengineered， 2022，13（4）：10111-10122.
［18］ Huang Yuhe， Hong Weiqi， Wei Xiawei. The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis［J］.J Hematol Oncol， 2022，15（1）：129.
［19］ Brabletz S， Schuhwerk H， Brabletz T， et al. Dynamic EMT： a multi-tool for tumor progression［J］.EMBO J， 2021，40（18）：e108647.
［20］ Feng Jing， Hu Shaofan， Liu Keli， et al. The role of microRNA in the regulation of tumor epithelial-mesenchymal transition［J］.Cells， 2022，11（13）：1981.
［21］ Deng Ziqin， Fan Tao， Xiao Chu， et al. TGF-beta signaling in health， disease， and therapeutics［J］.Signal Transduct Target Ther， 2024，9（1）：61.
［22］ Zhu Jihong， Wen Ke. Astragaloside IV inhibits TGF-beta1-induced epithelial-mesenchymal transition through inhibition of the PI3K/Akt/NF-kappaB pathway in gastric cancer cells［J］.Phytother Res， 2018，32（7）：1289-1296.
［23］ 陈凤琴，宁月，邵利华，等.黄芪甲苷通过调控TGF-β/Smad信号通路抑制胃癌的侵袭、迁移及上皮间质转化的研究［J］.中医药学报，2024，52（10）：16-24.
［24］ 曹艳，何利红，孙赟，等.黄芪甲苷对胃癌细胞SGC7901侵袭能力的影响及其机制探讨［J］.陕西医学杂志，2015，44（6）：656-659.
［25］ Auyeung KK， Woo PK， Law PC， et al. Astragalus saponins modulate cell invasiveness and angiogenesis in human gastric adenocarcinoma cells［J］.J Ethnopharmacol， 2012，141（2）：635-641.
［26］ Bejarano L， Jordao MJC， Joyce JA. Therapeutic targeting of the tumor microenvironment［J］.Cancer Discov， 2021，11（4）：933-959.
［27］ Bilotta MT， Antignani A， Fitzgerald DJ. Managing the TME to improve the efficacy of cancer therapy［J］.Front Immunol， 2022，13：954992.
［28］ Zhang Hao， Yue Xinghai， Chen Zhe， et al. Define cancer-associated fibroblasts （CAFs） in the tumor microenvironment： new opportunities in cancer immunotherapy and advances in clinical trials［J］.Mol Cancer， 2023，22（1）：159.
［29］ de Visser KE， Joyce JA. The evolving tumor microenvironment： from cancer initiation to metastatic outgrowth［J］.Cancer Cell， 2023，41（3）：374-403.
［30］ Sharma P， Siddiqui BA， Anandhan S， et al. The next decade of immune checkpoint therapy［J］.Cancer Discov， 2021，11（4）：838-857.
［31］ Wang Zhenfei， Ma Daguang， Zhu Zhe， et al. Astragaloside IV inhibits pathological functions of gastric cancer-associated fibroblasts［J］.World J Gastroenterol， 2017，23（48）：8512-8525.
［32］ Liu Haibo， Luo Shicheng， Sha Xiaofeng， et al. Astragaloside IV inhibits pathological functions of gastric cancer-associated fibroblasts through regulation of the HOXA6/ZBTB12 axis［J］.Acta Pharm， 2023，73（3）：423-439.
［33］ Liu Wei， Chen Han， Wang Dongsheng. Protective role of astragaloside IV in gastric cancer through regulation of microRNA-195-5p-mediated PD-L1［J］.Immunopharmacol Immunotoxicol， 2021，43（4）：443-451.
［34］ 曹丽萍，沈洪，刘丽，等.黄芪甲苷β-榄香烯对SGC7901胃癌细胞COX-2及PGE2表达的影响［J］.现代中西医结合杂志，2010，19（7）：798-800.
［35］ Romani AMP. Cisplatin in cancer treatment［J］.Biochem Pharmacol， 2022，206：115323.
［36］ Sethy C， Kundu CN. 5-Fluorouracil （5-FU） resistance and the new strategy to enhance the sensitivity against cancer： implication of DNA repair inhibition［J］.Biomed Pharmacother， 2021，137：111285.
［37］ Zhao Shuang， Tang Yufei， Wang Ruohan， et al. Mechanisms of cancer cell death induction by paclitaxel： an updated review［J］.Apoptosis， 2022，27（9-10）：647-667.
［38］ 叶青.黄芪甲苷对胃癌SGC7901/DDP细胞多药耐药性的逆转作用及其机制研究［D］.南京：南京中医药大学，2017.
［39］ 周坤.黄芪甲苷对胃癌细胞的作用效果及相关机制的研究［D］.石家庄：河北医科大学， 2016.
［40］ 李全志，郑林静，刘志强.黄芪甲苷Ⅳ联合紫杉醇通过STAT3-NF-κB途径对胃癌细胞的作用研究［J］.实用药物与临床，2022，25（1）：21-26.
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