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Reversal of Multidrug Resistance in an Epirubicin-Resistant Gastric Cancer Cell Subline

Aledson Vitor Felipe1,2, Juliana de Oliveira, Andrea Aparecida Moraes

  • 1Department of Medicine, Gastroenterology Division, Federal University of Sao Paulo, Brazil.

Asian Pacific Journal of Cancer Prevention : APJCP
|May 27, 2018
PubMed

Insights

Short interfering RNAs (siRNAs) effectively reduced ABCB1 gene expression in gastric cancer cells, overcoming epirubicin resistance. This targeted gene therapy approach enhances chemotherapy effectiveness by increasing drug sensitivity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Gastric cancer is a prevalent malignancy globally.
  • Epirubicin (EPI) is a key chemotherapy drug, but its efficacy is limited by multidrug resistance (MDR) due to ABCB1 efflux pump overexpression.
  • ABCB1 overexpression can be targeted by short interfering RNAs (siRNAs).

Purpose of the Study:

  • To investigate methods for reversing epirubicin resistance in gastric cancer.
  • To enhance chemotherapy success by targeting ABCB1 in an epirubicin-resistant gastric cancer cell line (AGS/EPI).

Main Methods:

  • Utilized siRNA technology for ABCB1 knockdown in AGS/EPI cells.
  • Employed quantitative real-time reverse-transcription PCR (qRT-PCR) for gene expression analysis.
  • Assessed cell viability and proliferation using MTT assays.
  • Visualized ABCB1 protein and epirubicin (EPI) intracellular localization via confocal microscopy.

Main Results:

  • siRNA successfully downregulated ABCB1 mRNA levels in AGS/EPI cells.
  • Demonstrated significant reversal of multidrug resistance (MDR) in the treated cells.
  • Observed decreased EPI efflux and increased EPI sensitivity in AGS/EPI cells post-ABCB1 knockdown.

Conclusions:

  • ABCB1 knockdown using siRNA is a viable strategy to overcome epirubicin resistance in gastric cancer.
  • This approach offers a novel targeted gene therapy for enhancing chemotherapy outcomes in gastric cancer patients.
  • The findings support the development of in vitro chemoresistance assays for gastric cancer research.
Keywords:
RNA interferencegastric cancerABCB1drug resistanceepirubicin

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