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Updated: Dec 7, 2025

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High Expression of p21 as a Potential Therapeutic Target in Ovarian Clear-cell Carcinoma

Yuki Minagawa1,2, Kousuke Ishino3, Ryuichi Wada1,4

  • 1Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo, Japan.

Anticancer Research
|September 29, 2020
PubMed
Abstract

Insights

Targeting p21, a key cell fate determinant in DNA damage response (DDR), shows promise for ovarian clear-cell carcinoma (CCC). Inhibiting p21 induced cell death in CCC cells with high p21 expression, suggesting a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • The DNA damage response (DDR) pathway is crucial in cancer, with p21 acting as a cell fate determinant.
  • Ovarian clear-cell carcinoma (CCC) presents a potential target for novel cancer therapies.
  • Understanding molecular expression during DDR in CCC is essential for therapeutic development.

Purpose of the Study:

  • To explore the molecular expression of DDR-associated molecules in ovarian clear-cell carcinoma (CCC).
  • To investigate the role of p21 as a potential therapeutic target in CCC.
  • To evaluate the efficacy of a p21 inhibitor in CCC cell lines.

Main Methods:

  • Immunostaining was used to examine the expression of CHK1, CHK2, TP53, and p21 in surgical sections of CCC (n=22).
  • Western blot analysis was performed to investigate molecular alterations in two CCC cell lines (JHOC-5 and JHOC-9).
  • The effect of a p21 inhibitor (UC2288) on cell proliferation, viability, and apoptosis was assessed.

Main Results:

  • DDR-associated molecules were expressed in most CCC patients studied.
  • Half of the patients showed high p21 expression, while the other half exhibited low p21 expression.
  • Treatment with the p21 inhibitor UC2288 reduced proliferation and induced apoptosis in both CCC cell lines, with a more pronounced effect in JHOC-9 cells.

Conclusions:

  • p21 inhibition effectively induced cell death in CCC cells with high p21 expression.
  • Suppression of p21 represents a potential therapeutic strategy for treating ovarian clear-cell carcinoma.
  • Further research into p21 targeted therapies for CCC is warranted.
Keywords:
DNA damage responseOvarian clear-cell carcinomacisplatinp21

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