β-arrestin 2 is associated with multidrug resistance in breast cancer cells through regulating MDR1 gene expression

摘要

Mutidrug resistance (MDR) severly blocks the successful management of breast cancer. Overexpression of MDR1/p-gp accounts for the major factor in the development of MDR. β-arrestin 2 has been reported to widely involve in multiple aspects of tumor development. In order to verify whether β-arrestin 2 regulates mutidrug resistance in breast cancer, we analyzed the protein expression levels of β-arrestin 2 and MDR1/p-gp by immunohistochemistry in 106 paraffin-embedded human breast tissue samples. There was a positive correlation between β-arrestin 2 and MDR1/p-gp protein expression (P = 0.016). Changes in MDR1/p-gp mRNA and protein levels were examined by quantitative real-time reverse polymerase chain reaction (qRT-PCR) and western blotting. Silencing of β-arrestin 2 evidently down-regulated the expression of MDR1/p-gp in transfected ADM cells. In contrast, overexpression of β-arrestin 2 had the opposite changes in MDA-MB-231 and MCF-7 cells. MTS assay revealed that silencing of β-arrestin 2 increased the sensitivity to anti-cancer drugs to some extent. On the other hand, overexpression of β-arrestin 2 had the opposite effects. Our above data demonstrate that β-arrestin 2 plays a vital role in the regulation of MDR1/p-gp expression in Breast cancer.