Overexpression of Survivin and XIAP in MDR cancer cells unrelated to P-glycoprotein

Abstract

Cancer cells developing multidrug resistance (MDR) is one of the most serious clinical problems responsible for the failure of cancer chemotherapy. P-glycoprotein (P-gp) overexpression and inhibitor of apoptosis proteins (IAPs) overexpression in cancer cells are the two common mechanisms of MDR. However, the relationship between IAPs and P-gp in MDR cancer cells is unknown. We investigated the expression levels of two IAPs, Survivin and XIAP, and their interaction with P-gp in MDR cancer cells. We have found that the human epidermoid carcinoma cells KBv200 and breast cancer cells MCF-7/Adr overexpress not only P-gp but also XIAP and Survivin, and showed high resistance to chemotherapeutic drugs doxorubicin, docetaxel and vincristine, in contrast to their parental cells KB and MCF-7. Furthermore, upregulation of Survivin or XIAP through transfection with the plasmid pECFPN1-Survivin or pcDNA3-6myc-XIAP in these four cell sublines did not affect the P-gp expression. Downregulation of Survivin or XIAP through transfection with the Survivin or XIAP siRNA did not have an effect on the P-gp expression in these resistant cells. Additionally, our immunoprecipitation results showed that Survivin or XIAP did not directly bind to P-gp. In summary, our study suggested that the overexpression of Survivin and XIAP in MDR cancer cells does not directly interact with P-gp.