Survivin transcription is associated with P-glycoprotein/MDR1 overexpression in the multidrug resistance of MCF-7 breast cancer cells

Abstract

Breast carcinoma is the most common malignancy in women. The progression of tumor is associated with overexpression of inhibitors of apoptosis proteins (IAPs) such as survivin and multidrug resistant P-glycoprotein (P-gp). PI3K/Akt pathway is involved in cell cycle progression, apoptosis and neoplastic transformation. PI3K/Akt has been shown to regulate survivin in breast cancer. The aim of this study was to investigate the expression of survivin and P-gp, the modulation of survivin by P-gp in PI3K/Akt during the progression of drug resistance (MDR) in MCF-7 breast cancer cells and adriamycin (ADR)-resistant MCF-7/ADR cells. The expression of survivin and P-gp in MCF-7/ADR cells were higher than that of the MCF-7 cells using RT-PCR and Western blot analysis. Survivin transcription was associated with P-glycoprotein/MDR1 overexpression using promoter activity analysis. LY294002, specific inhibitor of PI3K could suppress survivin and P-gp expression, decreased survivin promoter activity and enhanced cell sensitivity to drugs. This study shows survivin transcription was associated with P-glycoprotein/MDR1 overexpression, PI3k/Akt pathway was involved in P-glycoprotein/MDR1 associated survivin transcription activity in the multidrug resistant MCF-7 breast cancer cells.