STAT3小分子干扰RNA增强多柔比星的抗肿瘤活性  

Small interfering RNA targeting STAT3 enhances antitumor activity of doxorubicin

作　　者：王天晓[1] 王颖莹[1] 张中庆[1] 

机构地区：[1]河南大学中药研究所河南大学药学院,河南开封475004

出　　处：《药学学报》2013年第1期52-58,共7页Acta Pharmaceutica Sinica

基　　金：河南省教育厅自然科学研究项目(2011A310001)

摘　　要：探讨靶向STAT3的小分子干扰RNA(STAT3-siRNA)对多柔比星(doxorubicin,DOX)的抗肿瘤活性的影响。通过RT-PCR及Western blotting检测STAT3在HepG2、HeLa和K562/DOX细胞中的表达水平以及小分子干扰RNA对STAT3表达的影响。采用MTT法和台盼蓝染色法,检测STAT3-siRNA对肿瘤细胞的抑制作用及其对DOX抗肿瘤活性的影响。应用高内涵活细胞成像系统检测STAT3-siRNA对细胞内DOX蓄积量以及细胞凋亡的影响。结果显示,STAT3在HepG2、HeLa和K562/DOX细胞中均有高表达,STAT3-siRNA明显下调STAT3mRNA及STAT3蛋白的表达。STAT3-siRNA可抑制HepG2、HeLa和K562/DOX细胞的生长,STAT3-siRNA与DOX联合应用后对3种细胞的IC50分别降低了3.13倍、5.22倍和1.74倍(与DOX单独应用比较)。STAT3-siRNA使HepG2、HeLa及K562/DOX细胞内DOX的蓄积量分别增加16.8%、12.87%和25.67%,同时明显促进了DOX诱导的细胞凋亡。结果表明,STAT3-siRNA可明显增强DOX的抗肿瘤活性。This study is to investigate the effect of small interfering RNA targeting STAT3（STAT3-siRNA） enhancing antitumor activity of doxorubicin.RT-PCR and Western blotting were used to test the expression of STAT3 mRNA and protein in the HepG2,HeLa and K562/DOX cells and the effect of STAT3-siRNA on the expression of STAT3 mRNA and protein.MTT and Trypan blue assay were performed to determine the inhibitory effect of STAT3-siRNA on HepG2,HeLa and K562/DOX cells and the effect of STAT3-siRNA enhancing antitumor activity of doxorubicin.The effects of STAT3-siRNA on intracellular accumulation of doxorubicin and cell apoptosis were performed by Arrary Scan VTIHCS600 High-Contents.The results showed that STAT3 gene,STAT3 and pSTAT3 protein were highly expressed in HepG2,HeLa and K562/DOX cells and STAT3-siRNA decreased the expression of STAT3 mRNA and protein.STAT3-siRNA inhibited the growth of HepG2,HeLa and K562/DOX cells.STAT3-siRNA in combination with doxorubicin decreased by 3.13,5.22 and 1.74 fold of IC50of HepG2,HeLa and K562/DOX cells compared with doxorubicin only.Intracellular accumulation of doxorubicin increased by 16.8%,12.87% and 25.67% respectively in HepG2,HeLa and K562/DOX cells in the presence of STAT3-siRNA.An enhancement of doxorubicin-induced cell apoptosis was observed in HepG2,HeLa and K562/DOX cells treated with STAT3-siRNA.The results suggested that STAT3-siRNA could enhance the antitumor activity of doxorubicin on HepG2,HeLa and K562/DOX cells.

关 键 词：STAT3 小分子干扰RNA 肿瘤 多柔比星 高内涵成像系统 

分 类 号：R963[医药卫生—微生物与生化药学]