Cargando…

Apurinic endonuclease 1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin-mediated mitophagy

Platinum-containing doublet chemotherapy is the cornerstone of lung cancer treatment; however, cisplatin resistance is a major obstacle in the treatment of lung cancer. However, the mechanism underlying this resistance has not been fully elucidated. Previous studies have shown that serum apurinic/ap...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Zheng, Wang, Yongqiang, Wu, Linbo, Dong, Yalu, Zhang, Jing, Chen, Fan, Xie, Wei, Huang, Jianguo, Lu, Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826301/
https://www.ncbi.nlm.nih.gov/pubmed/31578585
http://dx.doi.org/10.3892/or.2019.7345
_version_ 1783465054094491648
author Li, Zheng
Wang, Yongqiang
Wu, Linbo
Dong, Yalu
Zhang, Jing
Chen, Fan
Xie, Wei
Huang, Jianguo
Lu, Ning
author_facet Li, Zheng
Wang, Yongqiang
Wu, Linbo
Dong, Yalu
Zhang, Jing
Chen, Fan
Xie, Wei
Huang, Jianguo
Lu, Ning
author_sort Li, Zheng
collection PubMed
description Platinum-containing doublet chemotherapy is the cornerstone of lung cancer treatment; however, cisplatin resistance is a major obstacle in the treatment of lung cancer. However, the mechanism underlying this resistance has not been fully elucidated. Previous studies have shown that serum apurinic/apyrimidinic endonuclease 1 (APE1) levels in patients with NSCLC are inversely associated with progression-free survival after platinum-containing doublet chemotherapy, and can serve as a biomarker for predicting disease prognosis and treatment efficacy. The present study was designed to investigate the role played by APE1 in the resistance of lung cancer to cisplatin. The levels of mitochondrial apurinic endonuclease 1 (m-APE1) and total APE1 (t-APE1) protein in a cisplatin-resistant A549 cell line (A549/DDP) and cisplatin-sensitive A549 cells were analyzed by western blotting. Mitochondrial membrane potential was detected by using the JC-1 staining method. The cisplatin-resistance of APE1-overexpressing A549 cells and APE1-silenced A549/DDP cells was assessed by cell apoptosis and colony formation assays. The results revealed that cisplatin-resistant A549 cells contained high levels of APE1, and exhibited elevated levels of autophagy. The levels of m-APE1 and t-APE1 protein were increased in the A549/DDP cells when compared with these levels in the A549 cells. Overexpression of APE1 and Mia40 enhanced the cisplatin resistance and autophagy of the A549 cells. APE1 knockdown restored the cisplatin sensitivity and reduced the levels of LC3II and Parkin in the A549/DDP cells, but promoted the release of cytochrome c. Furthermore, Parkin silencing or treatment with 3-methyladenine (3-MA, an autophagy inhibitor) promoted the apoptosis of APE1-overexpressing A549 cells, indicating that Parkin-mediated mitophagy plays an important role in the APE1-induced cisplatin resistance of A549 cells. In conclusion, APE1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin-mediated mitophagy.
format Online
Article
Text
id pubmed-6826301
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-68263012019-11-05 Apurinic endonuclease 1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin-mediated mitophagy Li, Zheng Wang, Yongqiang Wu, Linbo Dong, Yalu Zhang, Jing Chen, Fan Xie, Wei Huang, Jianguo Lu, Ning Oncol Rep Articles Platinum-containing doublet chemotherapy is the cornerstone of lung cancer treatment; however, cisplatin resistance is a major obstacle in the treatment of lung cancer. However, the mechanism underlying this resistance has not been fully elucidated. Previous studies have shown that serum apurinic/apyrimidinic endonuclease 1 (APE1) levels in patients with NSCLC are inversely associated with progression-free survival after platinum-containing doublet chemotherapy, and can serve as a biomarker for predicting disease prognosis and treatment efficacy. The present study was designed to investigate the role played by APE1 in the resistance of lung cancer to cisplatin. The levels of mitochondrial apurinic endonuclease 1 (m-APE1) and total APE1 (t-APE1) protein in a cisplatin-resistant A549 cell line (A549/DDP) and cisplatin-sensitive A549 cells were analyzed by western blotting. Mitochondrial membrane potential was detected by using the JC-1 staining method. The cisplatin-resistance of APE1-overexpressing A549 cells and APE1-silenced A549/DDP cells was assessed by cell apoptosis and colony formation assays. The results revealed that cisplatin-resistant A549 cells contained high levels of APE1, and exhibited elevated levels of autophagy. The levels of m-APE1 and t-APE1 protein were increased in the A549/DDP cells when compared with these levels in the A549 cells. Overexpression of APE1 and Mia40 enhanced the cisplatin resistance and autophagy of the A549 cells. APE1 knockdown restored the cisplatin sensitivity and reduced the levels of LC3II and Parkin in the A549/DDP cells, but promoted the release of cytochrome c. Furthermore, Parkin silencing or treatment with 3-methyladenine (3-MA, an autophagy inhibitor) promoted the apoptosis of APE1-overexpressing A549 cells, indicating that Parkin-mediated mitophagy plays an important role in the APE1-induced cisplatin resistance of A549 cells. In conclusion, APE1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin-mediated mitophagy. D.A. Spandidos 2019-12 2019-10-01 /pmc/articles/PMC6826301/ /pubmed/31578585 http://dx.doi.org/10.3892/or.2019.7345 Text en Copyright: © Li 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
Li, Zheng
Wang, Yongqiang
Wu, Linbo
Dong, Yalu
Zhang, Jing
Chen, Fan
Xie, Wei
Huang, Jianguo
Lu, Ning
Apurinic endonuclease 1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin-mediated mitophagy
title Apurinic endonuclease 1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin-mediated mitophagy
title_full Apurinic endonuclease 1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin-mediated mitophagy
title_fullStr Apurinic endonuclease 1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin-mediated mitophagy
title_full_unstemmed Apurinic endonuclease 1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin-mediated mitophagy
title_short Apurinic endonuclease 1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin-mediated mitophagy
title_sort apurinic endonuclease 1 promotes the cisplatin resistance of lung cancer cells by inducing parkin-mediated mitophagy
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826301/
https://www.ncbi.nlm.nih.gov/pubmed/31578585
http://dx.doi.org/10.3892/or.2019.7345
work_keys_str_mv AT lizheng apurinicendonuclease1promotesthecisplatinresistanceoflungcancercellsbyinducingparkinmediatedmitophagy
AT wangyongqiang apurinicendonuclease1promotesthecisplatinresistanceoflungcancercellsbyinducingparkinmediatedmitophagy
AT wulinbo apurinicendonuclease1promotesthecisplatinresistanceoflungcancercellsbyinducingparkinmediatedmitophagy
AT dongyalu apurinicendonuclease1promotesthecisplatinresistanceoflungcancercellsbyinducingparkinmediatedmitophagy
AT zhangjing apurinicendonuclease1promotesthecisplatinresistanceoflungcancercellsbyinducingparkinmediatedmitophagy
AT chenfan apurinicendonuclease1promotesthecisplatinresistanceoflungcancercellsbyinducingparkinmediatedmitophagy
AT xiewei apurinicendonuclease1promotesthecisplatinresistanceoflungcancercellsbyinducingparkinmediatedmitophagy
AT huangjianguo apurinicendonuclease1promotesthecisplatinresistanceoflungcancercellsbyinducingparkinmediatedmitophagy
AT luning apurinicendonuclease1promotesthecisplatinresistanceoflungcancercellsbyinducingparkinmediatedmitophagy