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Fatty acid oxidation inhibitor etomoxir suppresses tumor progression and induces cell cycle arrest via PPARγ-mediated pathway in bladder cancer.

Authors
  • Cheng, Songtao1
  • Wang, Gang2
  • Wang, Yejinpeng3
  • Cai, Liwei4
  • Qian, Kaiyu2
  • Ju, Lingao2
  • Liu, Xuefeng5
  • Xiao, Yu3
  • Wang, Xinghuan6
  • 1 Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, China. , (China)
  • 2 Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. , (China)
  • 3 Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. , (China)
  • 4 Department of Medicine, Nanchang University, Nanchang, China. , (China)
  • 5 Department of Pathology, Lombardi Comprehensive Cancer Center, Georgetown University Medical School, Washington DC, United States. , (United States)
  • 6 Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China [email protected] , (China)
Type
Published Article
Journal
Clinical Science
Publisher
Portland Press
Publication Date
Jul 29, 2019
Identifiers
DOI: 10.1042/CS20190587
PMID: 31358595
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Tumor cells rely on aerobic glycolysis as their main energy resource (Warburg effect). Recent researches highlighted the importance of lipid metabolism in tumor progression and certain cancers even turn to fatty acids as main fuel. Related studies have identified alterations of fatty acid metabolism in human bladder cancer (BCa). Our microarray analysis showed that fatty acid metabolism was activated in BCa compared with normal bladder. And the free fatty acid (FFA) level was increased in BCa compared with paracancerous tissues. Inhibition of FAO with etomoxir caused lipid accumulation, decreased adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH) level, suppressed BCa cell growth in vitro and in vivo, and reduced motility of BCa cells via affecting epithelial-mesenchymal transitions (EMT)-related proteins. Furthermore, etomoxir induced BCa cell cycle arrest at G0/G1 phase through PPARγ-mediated pathway with alterations in fatty acid metabolism associated gene expression. The cell cycle arrest could be reversed by PPARγ antagonist GW9662. Taken together, our results suggest that by inhibition of FAO with etomoxir may provide a novel avenue to investigate new therapeutic approaches to human BCa. ©2019 The Author(s).

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