二甲双胍抗肿瘤与 K－ras 突变的相关性

近年来，越来越多的研究表明，二甲双胍除了作为一种常用的降糖药物，还具有抗肿瘤作用。二甲双胍抗肿瘤作用机制包括：激活 AMPK 途径，促使细胞周期停滞，降低循环中胰岛素和 IGFs，自噬抗肿瘤，抑制肿瘤新生血管生成，杀灭肿瘤干细胞等。然而，二甲双胍抗肿瘤与基因突变是否相关还尚未明确。有研究证实，二甲双胍通过诱导细胞凋亡和抑制体内肿瘤细胞增殖的途径，能够有效地抑制 K －ras 突变型肿瘤细胞的生长，但并不抑制 K －ras 野生型肿瘤细胞的生长。因此，我们推论二甲双胍可作为 K －ras 突变型肿瘤的一个潜在的靶向药物。

The correlation between antitumor effects of metformin and K -ras gene mutation

In recent years,an increasing number of studies supported the use of metformin,a common antidiabetic drug,as a novel anticancer therapeutic.Its mechanism of action included the following aspects:Activate the AMPK pathway,block the cell cycle,regulate insulin/IGF -1 axis,regulate autophagy in tumor cells,inhibit tumor angiogen-esis,kill tumor stem cells,and so on.However,the correlation between the antitumor effects of metformin and gene mutations has not yet been identified.In the current study,metformin was observed to effectively inhibit the growth of the K -ras mutant but not wild type tumors.The antitumor effects of metformin were mediated by the induction of ap-optosis and inhibition of proliferation.Metformin was concluded to function as a potential K -ras targeting agent that had potential for cancer therapy.