二甲双胍在肿瘤治疗中的机制研究进展

The roles of metformin in anti-tumor therapy

作为胰岛素增敏剂的降糖药物二甲双胍具有抗肿瘤的多种生物活性,它能够抑制肿瘤细胞的增殖、促进凋亡、增强肿瘤对化疗药物的敏感性、并且能逆转部分肿瘤细胞对化疗药物的耐药性、甚至还能抑制肿瘤新生血管的生成。这些生物功能的实现依赖于AMPK等相关的信号通路的活化,进而负向调控mTOR通路信号分子的表达,再通过转录因子的表达调控相关靶基因的表达,因此这些信号分子的活化或抑制就成为了新的抗肿瘤治疗的靶点。肿瘤干细胞也是近年来研究的一个热点,二甲双胍能直接杀伤某些肿瘤的干细胞,从而达到有效抑瘤的作用,但二甲双胍杀伤肿瘤干细胞的分子机制不明确。另外,二甲双胍联合激素药物治疗肿瘤,可以增加保守治疗的效果。虽然二甲双胍具有显著的抗肿瘤的多重功效,但其具体的分子机制尚未被清晰完整的阐明,有待进一步的研究和证实。

Metformin,as a first line drugs for diabetes,plays an important role in anti-tumor therapy,which could attenuate the poliferative activity,promote tumor cells apoptosis,reverse parts of cancer cells＇resistance to chemotherapy,even inhibit tumor angiography.All above roles depend on the activiation of a certain signal pathways,such as AMPK,mTOR,and so on,and further mediate the targetting genes.Morever,metformin could kill the tumor stem cells,which is a hot project in cancer researching field.Although metformin serve so many roles,the detail molecular mechanism is not clear and need to be clarifed.