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β-elemene reverses chemoresistance of breast cancer via regulating MDR-related microRNA expression

Jun Zhang1, He da Zhang, Lin Chen

  • 1Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China.

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
|January 7, 2015
PubMed
Abstract

Insights

Beta-elemene reverses multidrug resistance (MDR) in breast cancer by altering miRNA expression and regulating PTEN and Pgp levels. This natural compound shows potential for overcoming chemotherapy failure in resistant breast cancer cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Multidrug resistance (MDR) is a major cause of chemotherapy failure in breast cancer (BCA).
  • Beta-elemene, a natural compound, has demonstrated MDR reversal capabilities.
  • This study investigates beta-elemene's effect on MDR in resistant human breast cancer cell lines (MCF-7/Adr and MCF-7/Doc) via gene regulatory networks.

Purpose of the Study:

  • To investigate the reversal effect of beta-elemene on multidrug resistance (MDR) in adriacin (Adr)-resistant and docetaxel (Doc)-resistant human breast cancer cells.
  • To explore the impact of beta-elemene on the gene regulatory network associated with chemoresistance.
  • To identify specific microRNAs (miRNAs) and their target genes involved in beta-elemene's MDR reversal mechanism.

Main Methods:

  • Cell viability assessed using MTT-cytotoxic assays.
  • miRNA expression profiling conducted via miRNA microarray and validated by Real-time quantitative PCR.
  • Downstream target gene (PTEN and Pgp) expression analyzed using Dual Luciferase Activity Assay and Western blot analysis.

Main Results:

  • Beta-elemene intervention (50μM/L for 30h) significantly altered miRNA expression profiles in both MCF-7/Adr and MCF-7/Doc cells.
  • Four specific miRNAs (miR-34a, miR-222, miR-452, and miR-29a) were identified as key players in mediating chemoresistance.
  • Beta-elemene treatment led to a significant increase in PTEN expression and a significant decrease in Pgp expression.

Conclusions:

  • Beta-elemene modulates the expression of MDR-related miRNAs.
  • The observed changes in miRNA expression subsequently regulate the expression of target genes PTEN and Pgp.
  • This mechanism contributes to the reduction of chemo-resistant breast cancer cell viability, suggesting beta-elemene's potential as a therapeutic agent.

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