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[Effects of miRNA-21 on paclitaxel-resistance in human breast cancer cells]

Zun-lan Zhao1, Ying Cai1, Yang-yang Wang1

  • 1Clinical Diagnosis Center, Bengbu Medical College, Bengbu 233000, China.

Zhejiang Da Xue Xue Bao. Yi Xue Ban = Journal of Zhejiang University. Medical Sciences
|November 12, 2015
PubMed
Abstract

Insights

Down-regulating miR-21 in paclitaxel-resistant breast cancer cells enhances sensitivity to the drug. This study establishes models for drug resistance research and identifies miR-21 as a key factor in paclitaxel resistance.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Pharmacology

Background:

  • Paclitaxel resistance is a major challenge in breast cancer treatment.
  • MicroRNAs (miRNAs) play crucial roles in drug resistance.
  • miR-21 has been implicated in various cancers, but its role in paclitaxel resistance needs further elucidation.

Purpose of the Study:

  • To investigate the role of miR-21 in paclitaxel resistance in human breast cancer cells.
  • To establish paclitaxel-resistant breast cancer cell lines as models for drug resistance studies.

Main Methods:

  • Established paclitaxel-resistant MCF-7/PR and SKBR-3/PR cell lines.
  • Assessed expression of multidrug resistance genes (MDR1, BCRP, MRP1) and apoptosis-related proteins (Bax, Bcl-2).
  • Utilized miR-21 inhibitors and mimics to modulate miR-21 levels and evaluated effects on cell viability, cell cycle, and apoptosis via MTT assays and flow cytometry.

Main Results:

  • Paclitaxel-resistant cells exhibited higher levels of MDR1, BCRP, MRP1, Bcl-2/Bax ratio, and miR-21 compared to parental cells.
  • Down-regulation of miR-21 using inhibitors decreased MDR1, BCRP, MRP1, and Bcl-2/Bax levels, suppressed cell cycle progression, induced apoptosis, and resensitized cells to paclitaxel.
  • miR-21 mimics increased MDR1 and Bcl-2/Bax expression, promoting a resistant phenotype.

Conclusions:

  • The established MCF-7/PR and SKBR-3/PR cell lines serve as effective models for studying multidrug resistance in breast cancer.
  • Down-regulated miR-21 expression significantly enhances the sensitivity of paclitaxel-resistant breast cancer cells to paclitaxel, highlighting miR-21 as a potential therapeutic target.

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