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. Materials/Methods: 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. Results: 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. Conclusion: 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.

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