A new contribution for an old drug: Prospect of metformin in colorectal oncotherapy

Metformin is well known as a hypoglycemic drug, which maintains glucose blood balance by attenuating hepatic glycogen synthesis and enhancing muscle glucose decomposition. The accumulation of epidemiologic studies demonstrates that metformin plays a beneficial role in preventing or treating colorectal carcinoma (CRC). Metformin intake alone or along with traditional chemotherapeutic drugs has been proved to attenuate the growth of colon cancer cells. The preventive or therapeutic efficiencies of metformin on CRC mainly include the following aspects: activating adenosine monophosphate-activated protein kinase/mammalian target of rapamycin pathway, inhibiting tumor angiogenesis, regulating immune response, enhancing cancer cells' sensitivity to chemotherapeutic agents, or inhibiting tumor stem cells. Therefore, metformin is suggested to become potential anticarcinoma agents. Nevertheless, the role of metformin in preventing and treating CRC is still controversial. In this review, we focused on the clinical value of metformin as a potentially effective anticarcinoma drug or an adjuvant agent, especially its mechanisms in CRC therapy.