Paxilitaxel induces apoptosis accompanied by protective autophagy in osteosarcoma cells through hypoxia-inducible factor-1α pathway.

Paxilitaxel, a drug used in cancer chemoprevention and treatment, has shown promising anti‑cancer effects against a broad spectrum of tumors. However, the effect of paxilitaxel on osteoblasts has remained to be elucidated. The aim of the present study was to investigate the anti‑tumor effect of paxilitaxel on human osteosarcoma cancer cells, the underlying molecular mechanism as well as drug resistance involved. The results showed that paxilitaxel not only induced apoptosis via the mitochondrial pathway but also induced autophagy, which partially inhibited cell apoptosis. The present study also demonstrated that paxilitaxel induced autophagy through the hypoxia‑inducible factor (HIF)‑1α pathway. Moreover, paxilitaxel‑induced apoptosis decreased following incubation with with the autophagy inducer rapamycin. By contrast, co‑treatment with the HIF‑1α inhibitor YC‑1 or autophagy inhibitor 3‑methyladenine significantly blocked autophagy and augmented the anti‑tumor effects of paxilitaxel. Therefore, the results of the present study suggested that the combination of paxilitaxel with an autophagy inhibitor or a HIF‑1α inhibitor may be an effective and potent strategy for improved chemotherapy of osteosarcoma in the future.