Reversal of multidrug resistance by small interfering RNA (siRNA) in doxorubicin-resistant MCF-7 breast cancer cells

Donmez Y., GÜNDÜZ U.

BIOMEDICINE & PHARMACOTHERAPY, vol.65, no.2, pp.85-89, 2011 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 65 Issue: 2
  • Publication Date: 2011
  • Doi Number: 10.1016/j.biopha.2010.12.007
  • Journal Name: BIOMEDICINE & PHARMACOTHERAPY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.85-89
  • Keywords: MDR reversal, P-glycoprotein, SiRNA, GENE-EXPRESSION, ABC-TRANSPORTERS, DRUG-RESISTANCE, P-GLYCOPROTEIN, CACO-2 CELLS, TUMOR-CELLS, MODULATION, MECHANISMS, MDR, SPECIFICITY
  • Middle East Technical University Affiliated: Yes

Abstract

Purpose: Resistance to anticancer drugs is a serious obstacle to cancer chemotherapy. A common form of multidrug resistance (MDR) is caused by the overexpression of transmembrane transporter proteins P-glycoprotein (P-gp) and multidrug resistance-associated protein-1 (MRP1), encoded by MDR1 and MRP1 genes, respectively. These proteins lead to reduced intracellular drug concentration and decreased cytotoxicity by means of their ability to pump the drugs out of the cells. Breast cancer tumor resistance is mainly associated with overexpression of P-gp/MDR1. Although some chemical MDR modulators aim to overcome MDR by interfering functioning of P-gp, their toxicities limit their usage in clinics. Consequently, RNA interference mediated sequence specific inhibition of the expression of P-gp/MDR1 mRNA may be an efficient tool to reverse MDR phenotype and increase the success of chemotherapy. Aim of this study was resensitizing doxorubicin-resistant breast cancer cells to anticancer agent doxorubicin by selective downregulation of P-gp/MDR1 mRNA.