Cargando…

Inhibition of Glucose-6-Phosphate Dehydrogenase Reverses Cisplatin Resistance in Lung Cancer Cells via the Redox System

The pentose phosphate pathway (PPP), which branches from glycolysis, is correlated with cancer cell proliferation, survival and senescence. In this study, differences in the metabolic profile of the PPP and the redox status of human lung carcinoma A549 cells and cisplatin-induced multidrug-resistant...

Descripción completa

Detalles Bibliográficos
Autores principales: Hong, Weipeng, Cai, Peiheng, Xu, Chuncao, Cao, Di, Yu, Weibang, Zhao, Zhongxiang, Huang, Min, Jin, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797786/
https://www.ncbi.nlm.nih.gov/pubmed/29445340
http://dx.doi.org/10.3389/fphar.2018.00043
_version_ 1783297750534717440
author Hong, Weipeng
Cai, Peiheng
Xu, Chuncao
Cao, Di
Yu, Weibang
Zhao, Zhongxiang
Huang, Min
Jin, Jing
author_facet Hong, Weipeng
Cai, Peiheng
Xu, Chuncao
Cao, Di
Yu, Weibang
Zhao, Zhongxiang
Huang, Min
Jin, Jing
author_sort Hong, Weipeng
collection PubMed
description The pentose phosphate pathway (PPP), which branches from glycolysis, is correlated with cancer cell proliferation, survival and senescence. In this study, differences in the metabolic profile of the PPP and the redox status of human lung carcinoma A549 cells and cisplatin-induced multidrug-resistant A549/DDP cells were analyzed and evaluated. The results showed that A549/DDP cells exhibited differential PPP-derived metabolic features and redox-related molecules. A549/DDP cells exhibited increased expression and enzymatic activity of PPP enzyme glucose-6-phosphate dehydrogenase (G6PD). Furthermore, as demonstrated by the apoptotic rate, cell viability, and colony formation, inhibition of G6PD by siRNA or an inhibitor sensitized A549/DDP cells to cisplatin. Additionally, inhibition of G6PD restored the cisplatin sensitivity of A549/DDP cells by influencing redox homeostasis. In conclusion, overcoming cisplatin resistance through inhibition of G6PD could improve the understanding of the mechanisms underlying cisplatin-induced resistance in human lung cancer and may provide insights into the therapeutic potential of this treatment to combat resistance.
format Online
Article
Text
id pubmed-5797786
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-57977862018-02-14 Inhibition of Glucose-6-Phosphate Dehydrogenase Reverses Cisplatin Resistance in Lung Cancer Cells via the Redox System Hong, Weipeng Cai, Peiheng Xu, Chuncao Cao, Di Yu, Weibang Zhao, Zhongxiang Huang, Min Jin, Jing Front Pharmacol Pharmacology The pentose phosphate pathway (PPP), which branches from glycolysis, is correlated with cancer cell proliferation, survival and senescence. In this study, differences in the metabolic profile of the PPP and the redox status of human lung carcinoma A549 cells and cisplatin-induced multidrug-resistant A549/DDP cells were analyzed and evaluated. The results showed that A549/DDP cells exhibited differential PPP-derived metabolic features and redox-related molecules. A549/DDP cells exhibited increased expression and enzymatic activity of PPP enzyme glucose-6-phosphate dehydrogenase (G6PD). Furthermore, as demonstrated by the apoptotic rate, cell viability, and colony formation, inhibition of G6PD by siRNA or an inhibitor sensitized A549/DDP cells to cisplatin. Additionally, inhibition of G6PD restored the cisplatin sensitivity of A549/DDP cells by influencing redox homeostasis. In conclusion, overcoming cisplatin resistance through inhibition of G6PD could improve the understanding of the mechanisms underlying cisplatin-induced resistance in human lung cancer and may provide insights into the therapeutic potential of this treatment to combat resistance. Frontiers Media S.A. 2018-01-31 /pmc/articles/PMC5797786/ /pubmed/29445340 http://dx.doi.org/10.3389/fphar.2018.00043 Text en Copyright © 2018 Hong, Cai, Xu, Cao, Yu, Zhao, Huang and Jin. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Hong, Weipeng
Cai, Peiheng
Xu, Chuncao
Cao, Di
Yu, Weibang
Zhao, Zhongxiang
Huang, Min
Jin, Jing
Inhibition of Glucose-6-Phosphate Dehydrogenase Reverses Cisplatin Resistance in Lung Cancer Cells via the Redox System
title Inhibition of Glucose-6-Phosphate Dehydrogenase Reverses Cisplatin Resistance in Lung Cancer Cells via the Redox System
title_full Inhibition of Glucose-6-Phosphate Dehydrogenase Reverses Cisplatin Resistance in Lung Cancer Cells via the Redox System
title_fullStr Inhibition of Glucose-6-Phosphate Dehydrogenase Reverses Cisplatin Resistance in Lung Cancer Cells via the Redox System
title_full_unstemmed Inhibition of Glucose-6-Phosphate Dehydrogenase Reverses Cisplatin Resistance in Lung Cancer Cells via the Redox System
title_short Inhibition of Glucose-6-Phosphate Dehydrogenase Reverses Cisplatin Resistance in Lung Cancer Cells via the Redox System
title_sort inhibition of glucose-6-phosphate dehydrogenase reverses cisplatin resistance in lung cancer cells via the redox system
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797786/
https://www.ncbi.nlm.nih.gov/pubmed/29445340
http://dx.doi.org/10.3389/fphar.2018.00043
work_keys_str_mv AT hongweipeng inhibitionofglucose6phosphatedehydrogenasereversescisplatinresistanceinlungcancercellsviatheredoxsystem
AT caipeiheng inhibitionofglucose6phosphatedehydrogenasereversescisplatinresistanceinlungcancercellsviatheredoxsystem
AT xuchuncao inhibitionofglucose6phosphatedehydrogenasereversescisplatinresistanceinlungcancercellsviatheredoxsystem
AT caodi inhibitionofglucose6phosphatedehydrogenasereversescisplatinresistanceinlungcancercellsviatheredoxsystem
AT yuweibang inhibitionofglucose6phosphatedehydrogenasereversescisplatinresistanceinlungcancercellsviatheredoxsystem
AT zhaozhongxiang inhibitionofglucose6phosphatedehydrogenasereversescisplatinresistanceinlungcancercellsviatheredoxsystem
AT huangmin inhibitionofglucose6phosphatedehydrogenasereversescisplatinresistanceinlungcancercellsviatheredoxsystem
AT jinjing inhibitionofglucose6phosphatedehydrogenasereversescisplatinresistanceinlungcancercellsviatheredoxsystem