title: Paxilitaxel induces apoptosis accompanied by protective autophagy in osteosarcoma cells through hypoxia-inducible factor-1α pathway.
abstract: 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.
authors.affiliation: Department of Orthopedics, The Fifth Affiliated Hospital of Sun Yat‑Sen University, Zhuhai, Guangdong 519000, P.R. China.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Orthopedics, The Fifth Affiliated Hospital of Sun Yat‑Sen University, Zhuhai, Guangdong 519000, P.R. China.
authors.forename: Chuangxin
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Orthopedics, The Fifth Affiliated Hospital of Sun Yat‑Sen University, Zhuhai, Guangdong 519000, P.R. China.
authors.forename: Guowei
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Orthopedics, The Fifth Affiliated Hospital of Sun Yat‑Sen University, Zhuhai, Guangdong 519000, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, The Fifth Affiliated Hospital of Sun Yat‑Sen University, Zhuhai, Guangdong 519000, P.R. China.
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopedics, The Fifth Affiliated Hospital of Sun Yat‑Sen University, Zhuhai, Guangdong 519000, P.R. China.
authors.forename: Zongwen
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017239:Paclitaxel