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[Suppression of WWOX gene by RNA interference reverses platinum resistance acquired in SKOV3/SB cells]

Yuan-Yuan Liu1, Li Li, Dan-Rong Li

  • 1Department of Gynecologic Oncology, Tumor Hospital, Guangxi Medical University, Nanning 530021, China.

Zhonghua Fu Chan Ke Za Zhi
|December 18, 2008
PubMed
Abstract

Insights

Small interference RNA (siRNA) effectively suppressed WWOX gene expression in SKOV3/SB cells. This suppression reduced cisplatin resistance and altered cell cycle distribution, suggesting WWOX

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • The WWOX gene plays a crucial role in tumor suppression.
  • Epithelial ovarian cancer (EOC) often exhibits resistance to chemotherapy, including cisplatin.
  • Understanding the mechanisms of cisplatin resistance is vital for improving EOC treatment outcomes.

Purpose of the Study:

  • To investigate the effect of WWOX gene suppression using small interference RNA (siRNA) in the SKOV3/SB ovarian cancer cell line.
  • To evaluate the impact of WWOX gene silencing on cisplatin resistance and cell cycle progression.

Main Methods:

  • Gene silencing was achieved by transfecting SKOV3/SB cells with WWOX-specific siRNA using Lipofectamine 2000.
  • WWOX mRNA and protein expression levels were quantified using RT-PCR and Western blot, respectively.
  • Cell cycle distribution was analyzed by flow cytometry (FCM).
  • Cisplatin resistance was assessed using the MTT assay, and cisplatin concentration was measured by HPLC.

Main Results:

  • WWOX gene expression was significantly reduced at both mRNA and protein levels in SKOV3/SB cells transfected with WWOX siRNA compared to controls (P < 0.05).
  • Transfection with WWOX siRNA led to a decrease in the cisplatin resistance index of SKOV3/SB cells (from 5.04 to 3.89).
  • Cells transfected with WWOX siRNA showed an increase in the G1 phase and a decrease in the S phase of the cell cycle.
  • The concentration of cisplatin in SKOV3/SB cells transfected with WWOX siRNA significantly increased (from 9.43 ng/L to 23.45 ng/L; P < 0.05).

Conclusions:

  • The WWOX gene is implicated in the cisplatin resistance observed in epithelial ovarian cancer.
  • Suppression of WWOX gene expression may represent a potential therapeutic strategy to overcome cisplatin resistance in ovarian cancer.

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