siRNA targeting ABCB1 potentiates the efficacy of chemotherapy in human triple-negative breast cancer cells

Abstract

Diminishing the efficacy of chemotherapy because of multidrug resistance (MDR) is a major clinical problem for triple-negative breast cancer (TNBC). MDR often occurs by overexpression of ATP-binding cassette B1 (ABCB1) protein that effuses various anticancer drugs from cancer cells. One of the newly developed techniques to addressing MDR is to knockdown ABCB1 by RNA interference (RNAi). RNAi is a gene-silencing process in that small interfering RNA (siRNA) blocks the expression of desired genes with high efficiency/specificity. The aim of this work is to examine the impact of ABCB1 inhibition via specific siRNAs on the efficacy of paclitaxel or etoposide in TNBC cells. The toxicity of increasing paclitaxel and etoposide concentrations on MDA-MB-231 cells was assessed using the MTT test. Cells were then co-treated with paclitaxel or etoposide in combination with ABCB1-siRNA, followed by cytotoxicity, colony formation, and migration assays. The administration of ABCB1-siRNA with paclitaxel or etoposide exhibited a synergistic effect and siRNA-drug treatments markedly reduced viability, clonogenicity, and migration of TNBC cells compared to siRNA or drug alone. Overall, these results indicate that TNBC cells become vulnerable even to sub-toxic doses of paclitaxel and etoposide after ABCB1-siRNA transfection, representing a promising aproach to enhance the influence of chemotherapy in TNBC.

Keywords

• Triple-negative breast cancer
• multidrug resistance
• chemotherapy
• siRNA

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