Metformin inhibits tumor growth and affects intestinal flora in diabetic tumor-bearing mice

Abstract

Many studies have found that diabetes increases the risk of some cancers such as hepatocellular carcinoma. However, there are few studies on the relationship between the two diseases and their effects on intestinal flora. Therefore, we used streptozotocin and high-fat diet to establish a mouse model of type 2 diabetes, and then inoculated the Huh-7 hepatocellular carcinoma cells to obtain mouse diabetic tumor model. Mice inoculated with Huh-7 cells alone served as control. The tumor size in the diabetic tumor group was significantly higher than that in the tumor group. Our study also showed that the expression levels of inflammation-related factors (TNFα, IL-1β, IL-6, TLR4 and MCP1) in the diabetic tumor group were significantly higher than that in the tumor group. We found that metformin alleviated blood glucose level, reduced the expressions of inflammation-related factors and retarded xenograft tumor growth in the diabetic tumor group, but it couldn't reduce the tumor growth in the tumor group. Subsequent studies found that the content of some short chain fatty acids (SCFAs) including acetic acid, propionic acid and isobutyric acid decreased significantly in diabetic tumor group. Metformin increased short chain fatty acid levels (acetic acid, butyic acid and valeric acid) and enriched the abundance of SCFA-producing bacterial genera such as Ruminococcaceae, Clostridiales, Anaerovorax, Odoribacter and Marvinbryantia. In conclusion, type 2 diabetes could promote the growth of hepatoma cells in mice. Metformin could inhibit the growth of tumor under the condition of diabetes and play a role in the intestinal homeostasis in mice.