Norcantharidin inhibits proliferation and promotes apoptosis via c‐Met/Akt/mTOR pathway in human osteosarcoma cells

Abstract

Osteosarcoma (OS) is the most common malignant bone tumor that frequently affects adolescents. Norcantharidin (NCTD), a demethylated derivative of cantharidin, has been reported exhibits anticancer activity against various types of tumors except human OS. The aims of this study were to evaluate the effects of NCTD on OS cell lines (MG63 and HOS) and to explore the underlying mechanisms. In the present study, the proliferation of OS cells decreased significantly, while the apoptosis was accelerated significantly after exposure to NCTD. Meanwhile, our results also indicated that NCTD could suppresses the migration and invasion, decrease the colony forming ability and induce S phase cell cycle arrest of OS cells in a dose‐dependent manner. Moreover, our results revealed that the anticancer effects induced by NCTD on OS cells involved autophagy, mitophagy, endoplasmic reticulum (ER) stress and c‐Met pathway. Furthermore, the results of animal experiments showed that NCTD inhibited tumor growth in a xenograft model of human OS. These evidences provide important new insight into the possible molecular mechanisms of NCTD and highlight its potential use as an antitumor drug for human OS.

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