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Regulation of HSF-1 by FBXW7 to Alleviate Multidrug Resistance in Ovarian Cancer

Fen Yang1, Yiran Xiao2, Xiaoni Zhou3

  • 1Department of Stomatology, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.

Current Cancer Drug Targets
|January 23, 2026
PubMed
Abstract

Insights

FBXW7 suppresses multidrug resistance in ovarian cancer by inhibiting the HSF-1/P-gp pathway. Restoring FBXW7 function may improve chemosensitivity and offer therapeutic benefits for epithelial ovarian cancer (EOC) patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Multidrug resistance (MDR) is a significant challenge in treating epithelial ovarian cancer (EOC).
  • The role of FBXW7 in regulating the HSF-1/P-glycoprotein (P-gp) signaling axis and its impact on MDR in ovarian cancer requires elucidation.

Purpose of the Study:

  • To investigate the regulatory role of FBXW7 in the HSF-1/P-gp signaling axis.
  • To determine the impact of FBXW7 on multidrug resistance in ovarian cancer.

Main Methods:

  • Quantitative PCR, western blotting, immunohistochemistry, and immunofluorescence were used to analyze FBXW7, HSF-1, and P-gp expression.
  • Functional assays including CCK-8 and lentiviral-mediated gene modulation were performed in ovarian cancer cell lines (SKOV3 and SKOV3/DDP).

Main Results:

  • FBXW7 expression was decreased in ovarian cancer tissues and correlated with poorer progression-free survival.
  • FBXW7 overexpression suppressed proliferation and decreased HSF-1/P-gp expression, while FBXW7 knockdown enhanced proliferation and upregulated the HSF-1/P-gp axis.
  • An inverse expression pattern between FBXW7 and HSF-1 was observed in patient tissues.

Conclusions:

  • FBXW7 suppresses MDR in ovarian cancer by downregulating the HSF-1/P-gp axis, enhancing chemosensitivity.
  • Restoring FBXW7 function presents a potential therapeutic strategy for overcoming chemoresistance in EOC.
  • This study provides mechanistic insights into chemoresistance and highlights FBXW7 as a therapeutic target.
Keywords:
E3 ubiquitin ligaseFBXW7HSF-1Multidrug resistanceP-gpchemoresistance.ovarian cancer

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