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Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death

  • Authors:
    • Ruichao Huo
    • Lili Wang
    • Peijuan Liu
    • Yong Zhao
    • Caiqin Zhang
    • Bing Bai
    • Xueying Liu
    • Changhong Shi
    • Sanhua Wei
    • Hai Zhang
  • View Affiliations / Copyright

    Affiliations: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China, Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Medicinal Chemistry, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
    Copyright: © Huo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3013-3020
    |
    Published online on: August 19, 2016
       https://doi.org/10.3892/mmr.2016.5648
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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.
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Copy and paste a formatted citation
Spandidos Publications style
Huo R, Wang L, Liu P, Zhao Y, Zhang C, Bai B, Liu X, Shi C, Wei S, Zhang H, Zhang H, et al: Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death. Mol Med Rep 14: 3013-3020, 2016.
APA
Huo, R., Wang, L., Liu, P., Zhao, Y., Zhang, C., Bai, B. ... Zhang, H. (2016). Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death. Molecular Medicine Reports, 14, 3013-3020. https://doi.org/10.3892/mmr.2016.5648
MLA
Huo, R., Wang, L., Liu, P., Zhao, Y., Zhang, C., Bai, B., Liu, X., Shi, C., Wei, S., Zhang, H."Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death". Molecular Medicine Reports 14.4 (2016): 3013-3020.
Chicago
Huo, R., Wang, L., Liu, P., Zhao, Y., Zhang, C., Bai, B., Liu, X., Shi, C., Wei, S., Zhang, H."Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death". Molecular Medicine Reports 14, no. 4 (2016): 3013-3020. https://doi.org/10.3892/mmr.2016.5648
Copy and paste a formatted citation
x
Spandidos Publications style
Huo R, Wang L, Liu P, Zhao Y, Zhang C, Bai B, Liu X, Shi C, Wei S, Zhang H, Zhang H, et al: Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death. Mol Med Rep 14: 3013-3020, 2016.
APA
Huo, R., Wang, L., Liu, P., Zhao, Y., Zhang, C., Bai, B. ... Zhang, H. (2016). Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death. Molecular Medicine Reports, 14, 3013-3020. https://doi.org/10.3892/mmr.2016.5648
MLA
Huo, R., Wang, L., Liu, P., Zhao, Y., Zhang, C., Bai, B., Liu, X., Shi, C., Wei, S., Zhang, H."Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death". Molecular Medicine Reports 14.4 (2016): 3013-3020.
Chicago
Huo, R., Wang, L., Liu, P., Zhao, Y., Zhang, C., Bai, B., Liu, X., Shi, C., Wei, S., Zhang, H."Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death". Molecular Medicine Reports 14, no. 4 (2016): 3013-3020. https://doi.org/10.3892/mmr.2016.5648
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