Inhibition of alternative cancer cell metabolism of egfr mutated non-small cell lung cancer serves as a potential therapeutic strategy

Chung Yu Huang, Li Han Hsu, Chung Yeh Chen, Gee Chen Chang, Hui Wen Chang, Yi Mei Hung, Ko Jiunn Liu, Shu Huei Kao

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Targeted therapy is an efficient treatment for patients with epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC). Therapeutic resistance invariably occurs in NSCLC patients. Many studies have focused on drug resistance mechanisms, but only a few have addressed the metabolic flexibility in drug-resistant NSCLC. In the present study, we found that during the developing resistance to tyrosine kinase inhibitor (TKI), TKI-resistant NSCLC cells acquired metabolic flexibility in that they switched from dependence on glycolysis to oxidative phosphorylation by substantially increasing the activity of the mitochondria. Concurrently, we found the predominant expression of monocarboxylate transporter 1 (MCT-1) in the TKI-resistant NSCLC cells was strongly increased in those cells that oxidized lactate. Thus, we hypothesized that inhibiting MCT-1 could represent a novel treatment strategy. We treated cells with the MCT-1 inhibitor AZD3965. We found a significant decrease in cell proliferation and cell motility in TKI-sensitive and TKI-resistant cells. Taken together, these results demonstrated that gefitinib-resistant NSCLC cells harbored higher mitochondrial bioenergetics and MCT-1 expression. These results implied that targeting mitochondrial oxidative phosphorylation proteins or MCT-1 could serve as potential treatments for both TKI-sensitive and –resistant non-small cell lung cancer.

Original languageEnglish
Article number181
JournalCancers
Volume12
Issue number1
DOIs
Publication statusPublished - Jan 2020

Keywords

  • Alternative metabolism
  • EGFR
  • Gefitinib-resistant
  • Monocarboxylate transporter 1
  • NSCLC

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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