Study of survivin-siRNA combined with the chemotherapy drugs to enhance the breast cancer MCF-7 cells apoptosis and reverse drug resistance / 肿瘤研究与临床

ABSTRACT

Objective To investigate the effects of siRNA against survivin combined with the neoadjuvant chemotherapy (paclitaxel and epirubicin) on the apoptosis in breast cancer MCF-7 cell and reverse drug resistance.Methods Molecular cloning technique was applied to construct the expression vector of siRNA against survivin,and effectene transfection reagent was used to transfect MCF-7 cell.Survivin expression was detected by qPCR and Western blot methods.The effects of paclitaxel or epirubicin combined with or without siRNA against survivin,on the drug susceptibility of MCF-7 cell were detected by CCK-8 assay and that of including MCF-7 cell apoptosis were detected by flow cytometry.Results Survivin-siRNA-2 effectively inhibited the expression of survivin mRNA (0.30±0.03) and protein (0.37±0.09) (P ＜ 0.05).Both paclitaxel [IR 24,48 h =(38.5±4.0) ％,(41.7±6.3) ％] and epirubicin [IR 24,48 h =(37.0±8.6) ％,(40.6± 12.1) ％] can suppress the proliferation of MCF-7 cell and induce its apoptosis,and siRNA against survivin combined with chemotherapy drugs enhanced both effects significantly[paclitaxel IR 24,48 h =(76.0±2.9) ％,(85.1±4.0) ％; epirubicin IR 24,48 h =(74.6±5.6) ％,(82.5±4.8) ％] (P ＜ 0.05).The inhibition rate of MCF-7 was concentration and time dependent.Conclusions Blocking survivin gene expression by RNAi,and combining with the appropriate chemotherapy can significantly enhance the sensitivity of MCF-7 cell to drugs and cell apoptosis.This technology has important potential clinical value in the therapy of breast cancer.