Research progress in antitumor mechanism of metformin independent of adenosine monophosphate activated protein kinase pathway / 中国药理学与毒理学杂志

ABSTRACT

Metformin is an oral hypoglycemic drug widely used in the treatment of type 2 diabetes mellitus. Epidemiological studies have showed that metformin is deeply involved in the prevention and treatment of cancer. And the antitumor mechanism of the effect of metformin has become a hot spot under intensive study. Most studies suggest that the pharmacological effect of metformin on cancer depends on the activation of adenosine monophosphate activated protein kinase (AMPK) pathway. Recently, some researchers proposed the anti-tumor mechanism of metformin through the AMPK independent pathway. Metformin affects the growth, invasion and migration of tumor cells by improving insulin sensitivity, down-regulating Ras-related GTP-binding protein Rag activity and the expressions of DNA damage response regulator gene 1 (Reddl), inhibiting the mammalian target of Rapamycin signaling pathways, and reducing the activity of Ras-related C3 botulinum toxin substrate and the protein expression of cell division cycle 42 and matrix metalloproteinases. In this paper, the antitumor effect and related mechanism of metformin independent of AMPK pathway are summarized, which offers a new perspective from which to explore the antitumor effect of metformin.