title: Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death.
abstract: Cabazitaxel has been used to treat castration-resistant prostate cancer since its approval by the US Food and Drug Administration in 2010. However, whether cabazitaxel may inhibit the proliferation of other tissue‑derived cancer cells, and its underlying mechanism, remains unknown. In the present study, the A549 lung adenocarcinoma cancer cell line was exposed to cabazitaxel, in order to investigate its cytotoxic effect and determine the underlying mechanism. The results demonstrated that cabazitaxel was able to induce autophagy in A549 cells, as evidenced by the formation of autophagosomes, upregulated LC3‑II expression and increased LC3 puncta. Cabazitaxel‑induced autophagy had a cytotoxic effect on A549 cells, as evidenced by the induction of cell death and cell cycle arrest at G2/M phase, which was independent of the apoptotic pathway. Furthermore, transfection with Beclin1 small interfering RNA and treatment with the autophagy inhibitor 3‑methyladenine protected cells from cabazitaxel‑induced cell death, thus confirming that cabazitaxel‑induced autophagy contributed to A549 cell death. In addition, cabazitaxel targeted the phosphoinositide 3‑kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway to induce autophagy, as indicated by reduced phosphorylation of Akt and mTOR. In conclusion, the present study demonstrated that cabazitaxel exerts a cytotoxic effect on A549 cells by acting on the PI3K/Akt/mTOR pathway to promote autophagic cell death. This result supports the potential use of cabazitaxel as a chemotherapeutic agent for the treatment of lung cancer.
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors: Ruichao
authors: R
authors: Huo
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors: Lili
authors: L
authors: Wang
authors: Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Peijuan
authors: P
authors: Liu
authors: Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Yong
authors: Y
authors: Zhao
authors: Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Caiqin
authors: C
authors: Zhang
authors: Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Bing
authors: B
authors: Bai
authors: Department of Medicinal Chemistry, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Xueying
authors: X
authors: Liu
authors: Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Changhong
authors: C
authors: Shi
authors: Department of Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors: Sanhua
authors: S
authors: Wei
authors: Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors: Hai
authors: H
authors: Zhang
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D043823:Taxoids; C552428:cabazitaxel; C546842:MTOR protein, human