Open AccessOpen Access

ARTICLE

PPARα activator irbesartan suppresses the proliferation of endometrial carcinoma cells via SREBP1 and ARID1A

YU LU1, TSUTOMU MIYAMOTO1,*, HODAKA TAKEUCHI1, FUMI TSUNODA1, NAOKI TANAKA2,3,4, TANRI SHIOZAWA1

1 Department of Obstetrics and Gynecology, School of Medicine, Shinshu University, Matsumoto, 390-8621, Japan
2 Department of Global Medical Research Promotion, School of Medicine, Shinshu University Graduate, Matsumoto, Nagano, 390-8621, Japan
3 International Relations Office, School of Medicine, Shinshu University, Matsumoto, Nagano, 390-8621, Japan
4 Research Center for Social Systems, Shinshu University, Matsumoto, Nagano, 390-8621, Japan

* Corresponding Author: TSUTOMU MIYAMOTO. Email:

Oncology Research 2023, 31(3), 239-253. https://doi.org/10.32604/or.2023.026067

Abstract

Endometrial carcinoma (EMC) is associated with obesity; however, the underlying mechanisms have not yet been elucidated. Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor that is involved in lipid, glucose, and energy metabolism. PPARα reportedly functions as a tumor suppressor through its effects on lipid metabolism; however, the involvement of PPARα in the development of EMC remains unclear. The present study demonstrated that the immunohistochemical expression of nuclear PPARα was lower in EMC than in normal endometrial tissues, suggesting the tumor suppressive nature of PPARα. A treatment with the PPARα activator, irbesartan, inhibited the EMC cell lines, Ishikawa and HEC1A, by down-regulating sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FAS) and up-regulating the tumor suppressor genes p21 and p27, antioxidant enzymes, and AT-rich interaction domain 1A (ARID1A). These results indicate the potential of the activation of PPARα as a novel therapeutic approach against EMC.

Keywords


Cite This Article

LU, Y., MIYAMOTO, T., TAKEUCHI, H., TSUNODA, F., TANAKA, N. et al. (2023). PPARα activator irbesartan suppresses the proliferation of endometrial carcinoma cells via SREBP1 and ARID1A. Oncology Research, 31(3), 239–253.



This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
  • 521

    View

  • 322

    Download

  • 1

    Like

Share Link