双胍类化合物抗肿瘤作用机制最新进展

Recent progress in the antitumor mechanisms of biguanides

近年来,多项研究证明双胍类化合物具有显著的抗肿瘤活性。其中,二甲双胍、苯乙双胍和氯胍作为双胍家族的代表性化合物,受到学者广泛关注。这些代表性化合物在体内及体外模型中均显示出良好的抗肿瘤活性,其机制研究涉及经典信号通路如抑制Complex Ⅰ和激活AMPK信号通路,也包括与肿瘤免疫微环境、肿瘤干细胞和铁死亡等相关的多种新的作用机制。因此,本综述旨在总结近年来双胍类化合物抗肿瘤作用机制的最新进展,为开发此类化合物用作临床抗肿瘤药物提供理论指导,并展望双胍类化合物在抗肿瘤领域面临的机遇与挑战。

In recent years, many studies have demonstrated that biguanides have significant antitumor activity. Among them, metformin, phenformin and proguanil, as representative compounds of the biguanide family, have received extensive attention from researchers. These representative compounds show excellent antitumor activity in vitro and in vivo models. Their antitumor mechanism involves the classical signaling pathway: inhibition of Complex I and activation of AMPK signaling pathway, as well as various novel mechanisms of action including tumor immune microenvironment, tumor stem cells and ferroptosis.Therefore, this review aims to summarize the latest progress in the mechanism of biguanides anti-tumor action in recent years and provide theoretical guidance for the development of such compounds as clinical antitumor drugs. Finally, we will look forward to the opportunities and challenges faced in the anti-tumor field of biguanides.