Metformin Inhibits Growth and Metastasis With Enhancement of Radiation Response in Hepatocellulcar Carcinoma Xenograft Model

Abstract

This study aimed to investigate the pntential of metformin to inhibits the growth and metastasis with enhancement of radiation response in hepatocellular carcinoma (HCC) xenograft mice model. Huh-7 HCC cells were injected to the right thigh in Balb/c nude mice. Huh-7 bearing mice were treated with local tumor irradiation with a single 15 Gy of X-ray (RT), intraperitoneal administration of metformin with 150 mg/kg/day until the day of sacrifice (MET), or combination of both (administration of metformin 6 hours prior irradiation) (RT-MET). Tumor response to treatment was determined by a tumor growth delay assay. Metastatic potential was evaluated by gross qualitative observation of spontaneous pulmonary metastasis in a lung metastasis model on day 45 and 60. RT or MET resulted in a significant reduction of tumor growth and RT-MET enhanced it further than each treatment alone (55% reduction compared with RT and 67% reduction compared with MET). More importantly, RT or MET inhibited in the growth of metastatic nodules in lung and RT-MET enhanced it further than each treatment alone (93% reduction compared with RT and 76% reduction compared with MET). RT-MET decreased the expression of vascular endothelial growth factor and matrix metallopeptidase 9 by immunohistochemistry. Metformin inhibits the growth and metastasis of HCC with enhancement of radiation response in vivo. Our data suggest that metformin can be a clinically useful adjunct to radiotherapy in HCC.