Investigational New Drugs

, Volume 28, Issue 6, pp 783–790

DH9, a novel PPARγ agonist suppresses the proliferation of ADPKD epithelial cells: An association with an inhibition of β-catenin signaling

  • Moyan Liu
  • Lili Fu
  • Chunyan Liu
  • Xishan Xiong
  • Xiang Gao
  • Min Xiao
  • Houan Cai
  • Huimin Hu
  • Xueqi Wang
  • Changlin Mei
PRECLINICAL STUDIES

Summary

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease that exclusively progresses to renal failure. An important target for the treatment of ADPKD is to reduce cystic cell proliferation. PPARγ agonists such as TZDs are insulin sensitizing agents that have also been reported to decrease tumor growth. Here we tested DH9, a newly synthesized PPARγ agonist on the proliferation of an ADPKD cell line, WT9-12. DH9 showed a potent anti-proliferative activity against ADPKD cells. At high concentration, DH9 also induced apoptotic cell death. The effect of DH9 on cell proliferation was mediated by a PPARγ independent mechanism. Since DH9 decreased the levels of β-catenin in cells via a GSK3β mediated degradation pathway, this acts as a mechanism for growth inhibition by DH9.

Keywords

ADPKD PPARγ α-aryloxy-α-methylhydrocinnamic acid derivative β-catenin GSK3β 

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Moyan Liu
    • 1
  • Lili Fu
    • 1
  • Chunyan Liu
    • 1
  • Xishan Xiong
    • 1
  • Xiang Gao
    • 1
  • Min Xiao
    • 1
  • Houan Cai
    • 1
  • Huimin Hu
    • 1
  • Xueqi Wang
    • 1
  • Changlin Mei
    • 1
  1. 1.Nephrology institute of PLA, Department of Internal Medicine, Changzheng HospitalSecond Military Medical UniversityShanghaiPeople’s Republic of China

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