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

Document Type: Research Articles

Authors

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

2 Department of Health, University Nove de Julho, College of Pharmacy, Sao Paulo, Brazil.

3 Department of Biological Sciences, Estadual University of Santa Cruz, Bahia, Brazil.

Abstract

Background: Gastric cancer is one of the most common malignancies worldwide. Epirubicin (EPI) is used
extensively in the treatment of multiple cancers despite its tendency to induce multidrug resistance though overexpression
of the ABCB1 efflux pump. However, this overexpression can be disrupted using short interfering RNAs (siRNAs).
Objective and Methods: The aim of this study was to explore approaches to reverse EPI resistance and thus increase
the success of chemotherapy treatment in an EPI-resistant gastric cancer cell subline (AGS/EPI). Methods: The study
focused on effects of ABCB1 knockdown by siRNA technology using TaqMan gene expression assays with quantitative
real-time reverse-transcription PCR (qRT-PCR). MTT assays were performed to evaluate viability and prolifer in subline.
ABCB1 protein localization and EPI intracellular fluorescence intensity in AGS/EPI cells were detected by confocal
microscopy. Results: The siRNA efficiently downregulated ABCB1 mRNA in AGS/EPI cells. Thus MDR reversal
was clearly demonstrated in the AGS/EPI cells, offering the possibility of future in vitro chemoresistance assays for
the GC field. Conclusions: ABCB1 knockdown decreased EPI efflux and increased EPI sensitivity in AGS/EPI cells.
This result provides a novel strategy for targeted gene therapy to reverse EPI resistance in gastric cancer.

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