Radiosensitizing potential of Phenformin in a preclinical colorectal cancer model.

Biguanides, used for anti-diabetic drugs, bring more attention in cancer research for their beneficial effects. Phenformin is a more potent drug than the widely used metformin. In this study we investigated the beneficial effect of Phenformin and radiotherapy on colorectal cancer. Phenformin may exert antitumor effects via inhibition of AMPK. Moreover, it may improve tumor oxygenation via inhibition of the mitochondrial complex I. Colorectal cancer cell lines were subjected to metabolic hypoxia and analyzed for radiosensitivity by clonogenic assay. Their oxygen consumption was measured by Seahorse and expression of AMPK by Western blotting. Furthermore, were colorectal cancer cells injected in Balb/c mice and treated with Phenformin through oral gavage in combination or alone with radiation therapy. Phenformin has a clear radiosensitizing effect both in vitro as in vivo on colorectal cancer cell lines.