二甲双胍已被用于治疗2型糖尿病，越来越多的研究表明，二甲双胍可以单独作用或与其他抗癌药物协同作用，以达到对各种类型肿瘤的抗癌功效。然而，二甲双胍在诱导人胃癌（GC）细胞自噬和顺铂耐药中的作用尚未得到研究。该研究建立了顺铂耐药的GC细胞系，并研究了二甲双胍对其诱导自噬的影响。结果表明，二甲双胍治疗可以浓度依赖性地抑制顺铂耐药GC细胞的细胞活力和细胞汇合，同时对人原代胃上皮细胞（HPSEC）没有影响。我们首次发现二甲双胍可以显着增加顺铂耐药GC细胞中酸性囊泡细胞器（AVO）水平并降低吖啶橙（AO）水平。因此，我们进一步检查了其他标记物Atg5、Atg12和LC3-II，这表明二甲双胍确实诱导了顺铂耐药GC细胞的自噬。此外，3-甲基腺嘌呤（3-MA）的治疗可以显着挽救二甲双胍诱导的自噬。同时，二甲双胍可以诱导凋亡相关信号分子的改变，例如caspase-3和caspase-7活性。总体而言，该初步研究为二甲双胍除了诱导细胞凋亡外还诱导自噬提供了证据，使其成为治疗顺铂耐药GC的有效抗癌药物。使用无毒的二甲双胍通过自噬和细胞凋亡杀死顺铂耐药的胃癌细胞，可能会扩大其在对抗胃癌细胞化疗耐药性方面的用途。© 作者。

Metformin has been used to treat cases of type 2 diabetes mellitus, and mounting studies have shown that metformin can act alone or in synergy with other anticancer agents to achieve anti-cancer efficacies on various types of tumors. However, the role of metformin in either inducing autophagy and cisplatin-resistance of human gastric cancer (GC) cells has never been examined. The study has established a cisplatin-resistant GC cell line and investigated the effects of metformin on inducing autophagy on it. The results demonstrated that treatment with metformin can concentration-dependently suppress the cell viability and cell confluence of cisplatin-resistant GC cells, while having no effects on human primary stomach epithelial cells (HPSEC). For the first time, we found that metformin can significantly increase the acidic vesicular organelles (AVO) level and decrease the acridine orange (AO) level spontaneously in the cisplatin-resistant GC cells. Thus, we further checked the other markers, Atg5, Atg12 and LC3-II, which showed that metformin indeed induced autophagy in the cisplatin-resistant GC cells. In addition, treatment of 3-Methyladenine (3-MA) can significantly rescue the metformin-induced autophagy. At the same time, metformin can induce the alterations of apoptosis-associated signal molecules, such as caspase-3 and caspase-7 activities. Overall, the pilot study provided evidence for metformin induced autophagy in addition to apoptosis, making it as an effective anticancer drug for the therapy of cisplatin-resistant GC. Killing the cisplatin-resistant GC cells with non-toxic metformin via both autophagy and apoptosis might extend its usefulness in our fighting with chemo-resistance of gastric cancer cells.© the Author(s).