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

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 st...

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Autores principales: Huo, Ruichao, Wang, Lili, Liu, Peijuan, Zhao, Yong, Zhang, Caiqin, Bai, Bing, Liu, Xueying, Shi, Changhong, Wei, Sanhua, Zhang, Hai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042750/
https://www.ncbi.nlm.nih.gov/pubmed/27572899
http://dx.doi.org/10.3892/mmr.2016.5648
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author Huo, Ruichao
Wang, Lili
Liu, Peijuan
Zhao, Yong
Zhang, Caiqin
Bai, Bing
Liu, Xueying
Shi, Changhong
Wei, Sanhua
Zhang, Hai
author_facet Huo, Ruichao
Wang, Lili
Liu, Peijuan
Zhao, Yong
Zhang, Caiqin
Bai, Bing
Liu, Xueying
Shi, Changhong
Wei, Sanhua
Zhang, Hai
author_sort Huo, Ruichao
collection PubMed
description 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 G(2)/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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spelling pubmed-50427502016-10-05 Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death Huo, Ruichao Wang, Lili Liu, Peijuan Zhao, Yong Zhang, Caiqin Bai, Bing Liu, Xueying Shi, Changhong Wei, Sanhua Zhang, Hai Mol Med Rep Articles 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 G(2)/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. D.A. Spandidos 2016-10 2016-08-19 /pmc/articles/PMC5042750/ /pubmed/27572899 http://dx.doi.org/10.3892/mmr.2016.5648 Text en Copyright: © Huo et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Huo, Ruichao
Wang, Lili
Liu, Peijuan
Zhao, Yong
Zhang, Caiqin
Bai, Bing
Liu, Xueying
Shi, Changhong
Wei, Sanhua
Zhang, Hai
Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death
title Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death
title_full Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death
title_fullStr Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death
title_full_unstemmed Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death
title_short Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death
title_sort cabazitaxel-induced autophagy via the pi3k/akt/mtor pathway contributes to a549 cell death
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042750/
https://www.ncbi.nlm.nih.gov/pubmed/27572899
http://dx.doi.org/10.3892/mmr.2016.5648
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