Affiliation:
1. Cancer Centre, Faculty of Health Sciences University of Macau, Avenida de Universidade China
2. School of Pharmaceutical Sciences, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research Chongqing University China
Abstract
Lung cancer cells often show elevated levels of reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH). However, the connections between deregulated redox homeostasis in different subtypes of lung cancer and acquired drug resistance in lung cancer have not yet been fully established. Herein, we analyzed different subtypes of lung cancer data reported in the Cancer Cell Line Encyclopedia (CCLE) database, the Cancer Genome Atlas program (TCGA), and the sequencing data obtained from a gefitinib‐resistant non‐small‐cell lung cancer (NSCLC) cell line (H1975GR). Using flux balance analysis (FBA) model integrated with multiomics data and gene expression profiles, we identified cytosolic malic enzyme 1 (ME1) and glucose‐6‐phosphate dehydrogenase as the major contributors to the significantly upregulated NADPH flux in NSCLC tissues as compared with normal lung tissues, and gefitinib‐resistant NSCLC cell line as compared with the parental cell line. Silencing the gene expression of either of these two enzymes in two osimertinib‐resistant NSCLC cell lines (H1975OR and HCC827OR) exhibited strong antiproliferative effects. Our findings not only underscored the pivotal roles of cytosolic ME1 and glucose‐6‐phosphate dehydrogenase in regulating redox states in NSCLC cells but also provided novel insights into their potential roles in drug‐resistant NSCLC cells with disturbed redox states.
Funder
Fundo para o Desenvolvimento das Ciências e da Tecnologia
Universidade de Macau
Subject
Cell Biology,Molecular Biology,Biochemistry
Reference74 articles.
1. Global cancer statistics, 2012
2. HowladerN NooneA KrapchoM MillerD BrestA YuM RuhlJ TatalovichZ MariottoA&LewisD(2020)SEER Cancer Statistics Review 1975–2016. National Cancer Institute. Bethesda MD Based on November 2018 SEER Data Submission Posted to the SEER Web Site April 2019.https://seer.cancer.gov/csr/1975_2018/Accessed 30 Jun 2021
3. Lung Cancer: Understanding Its Molecular Pathology and the 2015 WHO Classification
4. The Effect of Advances in Lung-Cancer Treatment on Population Mortality
5. Introduction to The 2015 World Health Organization Classification of Tumors of the Lung, Pleura, Thymus, and Heart
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献