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Protective autophagy antagonizes oxaliplatin-induced apoptosis in gastric cancer cells

Oxaliplatin-based chemotherapy is used for treating gastric cancer. Autophagy has been extensively implicated in cancer cells; however, its function is not fully understood. Our study aimed to determine if oxaliplatin induce autophagy in gastric cancer MGC803 cells and to assess the effect of autoph...

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Autores principales: Xu, Ling, Qu, Xiu-Juan, Liu, Yun-Peng, Xu, Ying-Ying, Liu, Jing, Hou, Ke-Zuo, Zhang, Ye
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Sun Yat-sen University Cancer Center 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013424/
https://www.ncbi.nlm.nih.gov/pubmed/21718595
http://dx.doi.org/10.5732/cjc.010.10518
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author Xu, Ling
Qu, Xiu-Juan
Liu, Yun-Peng
Xu, Ying-Ying
Liu, Jing
Hou, Ke-Zuo
Zhang, Ye
author_facet Xu, Ling
Qu, Xiu-Juan
Liu, Yun-Peng
Xu, Ying-Ying
Liu, Jing
Hou, Ke-Zuo
Zhang, Ye
author_sort Xu, Ling
collection PubMed
description Oxaliplatin-based chemotherapy is used for treating gastric cancer. Autophagy has been extensively implicated in cancer cells; however, its function is not fully understood. Our study aimed to determine if oxaliplatin induce autophagy in gastric cancer MGC803 cells and to assess the effect of autophagy on apoptosis induced by oxaliplatin. MGC803 cells were cultured with oxaliplatin. Cell proliferation was measured using MTT assay, and apoptosis was determined by flow Cytometry. Protein expression was detected by Western blot. Autophagy was observed using fluorescent microscopy. Our results showed that the rate of apoptosis was 9.73% and 16.36% when MGC803 cells were treated with 5 and 20 µg/mL oxaliplatin for 24 h, respectively. In addition, Caspase activation and poly ADP-ribose polymerase (PARP) cleavage were detected. Furthermore, when MGC803 cells were treated with oxaliplatin for 24 h, an accumulation of punctate LC3 and an increase of LC3-II protein were also detected, indicating the activation of autophagy. Phosphorylation of Akt and mTOR were inhibited by oxaliplatin. Compared to oxaliplatin alone, the combination of autophagy inhibitor chlorochine and oxaliplatin significantly enhanced the inhibition of cell proliferation and the induction of cell apoptosis. In conclusion, oxaliplatin-induced protective autophagy partially prevents apoptosis in gastric cancer MGC803 cells. The combination of autophagy inhibitor and oxaliplatin may be a new therapeutic option for gastric cancer.
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spelling pubmed-40134242014-05-15 Protective autophagy antagonizes oxaliplatin-induced apoptosis in gastric cancer cells Xu, Ling Qu, Xiu-Juan Liu, Yun-Peng Xu, Ying-Ying Liu, Jing Hou, Ke-Zuo Zhang, Ye Chin J Cancer Original Article Oxaliplatin-based chemotherapy is used for treating gastric cancer. Autophagy has been extensively implicated in cancer cells; however, its function is not fully understood. Our study aimed to determine if oxaliplatin induce autophagy in gastric cancer MGC803 cells and to assess the effect of autophagy on apoptosis induced by oxaliplatin. MGC803 cells were cultured with oxaliplatin. Cell proliferation was measured using MTT assay, and apoptosis was determined by flow Cytometry. Protein expression was detected by Western blot. Autophagy was observed using fluorescent microscopy. Our results showed that the rate of apoptosis was 9.73% and 16.36% when MGC803 cells were treated with 5 and 20 µg/mL oxaliplatin for 24 h, respectively. In addition, Caspase activation and poly ADP-ribose polymerase (PARP) cleavage were detected. Furthermore, when MGC803 cells were treated with oxaliplatin for 24 h, an accumulation of punctate LC3 and an increase of LC3-II protein were also detected, indicating the activation of autophagy. Phosphorylation of Akt and mTOR were inhibited by oxaliplatin. Compared to oxaliplatin alone, the combination of autophagy inhibitor chlorochine and oxaliplatin significantly enhanced the inhibition of cell proliferation and the induction of cell apoptosis. In conclusion, oxaliplatin-induced protective autophagy partially prevents apoptosis in gastric cancer MGC803 cells. The combination of autophagy inhibitor and oxaliplatin may be a new therapeutic option for gastric cancer. Sun Yat-sen University Cancer Center 2011-07 /pmc/articles/PMC4013424/ /pubmed/21718595 http://dx.doi.org/10.5732/cjc.010.10518 Text en Chinese Journal of Cancer http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission.
spellingShingle Original Article
Xu, Ling
Qu, Xiu-Juan
Liu, Yun-Peng
Xu, Ying-Ying
Liu, Jing
Hou, Ke-Zuo
Zhang, Ye
Protective autophagy antagonizes oxaliplatin-induced apoptosis in gastric cancer cells
title Protective autophagy antagonizes oxaliplatin-induced apoptosis in gastric cancer cells
title_full Protective autophagy antagonizes oxaliplatin-induced apoptosis in gastric cancer cells
title_fullStr Protective autophagy antagonizes oxaliplatin-induced apoptosis in gastric cancer cells
title_full_unstemmed Protective autophagy antagonizes oxaliplatin-induced apoptosis in gastric cancer cells
title_short Protective autophagy antagonizes oxaliplatin-induced apoptosis in gastric cancer cells
title_sort protective autophagy antagonizes oxaliplatin-induced apoptosis in gastric cancer cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013424/
https://www.ncbi.nlm.nih.gov/pubmed/21718595
http://dx.doi.org/10.5732/cjc.010.10518
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