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Dysregulated BARD1 Contributes to Paclitaxel Resistance in Ovarian Cancer via Up-regulating CYP2C8

Li Zhang1, Zixuan Pan1, Liqin Zhang2

  • 1Gynecology Department 1, Affiliated Hospital of Shandong Second Medical University, Weifang, China.

Folia Biologica
|October 30, 2025
PubMed

Insights

Lower BARD1 levels in ovarian cancer (OC) correlate with paclitaxel resistance. Restoring BARD1 may overcome resistance, offering a new therapeutic target for this lethal gynaecological malignancy.

Area of Science:

  • Oncology
  • Gynaecology
  • Pharmacology

Background:

  • Ovarian cancer (OC) is a leading cause of gynaecological cancer death.
  • Paclitaxel resistance significantly limits treatment efficacy and patient survival in OC.
  • The role of BARD1 in OC paclitaxel sensitivity is not well understood.

Purpose of the Study:

  • To investigate the relationship between BARD1 expression and paclitaxel sensitivity in OC.
  • To elucidate the mechanism by which BARD1 influences paclitaxel resistance.
  • To identify BARD1 as a potential therapeutic target for overcoming paclitaxel resistance in OC.

Main Methods:

  • Analysis of BARD1 expression in OC tumor samples from paclitaxel responders and non-responders.
  • Correlation analysis between BARD1 and CYP2C8 expression.
  • In vitro functional experiments (overexpression and knockdown) of BARD1 in OC cells.
  • Assessment of paclitaxel IC50 values following BARD1 manipulation.

Main Results:

  • BARD1 levels were significantly reduced in paclitaxel non-responders compared to responders.
  • CYP2C8 expression was upregulated in non-responders and negatively correlated with BARD1 levels.
  • BARD1 downregulation increased paclitaxel IC50 values in OC cell lines, indicating enhanced resistance.
  • BARD1 functions as a tumor suppressor in the context of paclitaxel treatment.

Conclusions:

  • Downregulation of BARD1 contributes to paclitaxel resistance in ovarian cancer by upregulating CYP2C8.
  • BARD1 acts as a tumor suppressor and its reduced expression is linked to poorer treatment outcomes.
  • Targeting BARD1 or modulating its pathway presents a promising strategy for overcoming paclitaxel resistance in OC.
Keywords:
BARD1CYP2C8ovarian cancerpaclitaxelresistance

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