[Antisense oligonucleotide reverses topotecan-resistant ovarian cancer cells]

Ping Jia1, Shao-Bo Wu, Qian Xu

  • 1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.

Abstract

Insights

Antisense oligonucleotide (ASODN) targeting breast cancer resistance protein (BCRP) reduced BCRP mRNA levels in ovarian cancer cells. This reversal of BCRP-mediated drug resistance improved sensitivity to topotecan.

Area of Science:

  • Molecular Biology
  • Pharmacology
  • Oncology

Background:

  • Breast cancer resistance protein (BCRP) overexpression is linked to topotecan resistance in ovarian cancer.
  • BCRP plays a significant role in mediating drug resistance in ovarian cancer cells.

Purpose of the Study:

  • To investigate the reversal effect of BCRP antisense oligonucleotide (ASODN) on topotecan-resistant A2780/TPT ovarian cancer cells.
  • To evaluate the potential of ASODN in overcoming BCRP-mediated drug resistance.

Main Methods:

  • Synthesis of BCRP antisense oligonucleotide (ASODN) and sense oligonucleotide (SODN) as control.
  • Lipofect-2000 (LF) mediated transfection of ASODN/SODN into A2780/TPT cells.
  • Assessment of BCRP mRNA expression (RT-PCR), intracellular rhodamine fluorescence (FCM), and topotecan resistance (MTT assay).

Main Results:

  • ASODN transfection significantly reduced BCRP mRNA levels by 59.42% (P<0.05).
  • Intracellular rhodamine fluorescence intensity increased significantly post-ASODN transfection (from 5.42 to 16.63, P<0.05).
  • Topotecan resistance index decreased from 25 to 5, indicating restored sensitivity in A2780/TPT cells; SODN transfection showed no significant changes.

Conclusions:

  • ASODN transfection demonstrates a capacity to partially reverse BCRP-mediated drug resistance in ovarian cancer cells.
  • Targeting BCRP with ASODN offers a potential strategy to enhance the efficacy of topotecan in ovarian cancer treatment.

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