桔梗皂苷D联合伊马替尼对K562细胞的增殖抑制作用及机制研究  

Effect of platycodin D combined with imatinib on K562 cell in vitro

作　　者：代群[1] 葛宇清[1] DAI Qun GE Yuqing(Central Laboratory of First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou310006, China)

机构地区：[1]浙江中医药大学附属第一医院中心实验室,杭州310006

出　　处：《浙江医学》2017年第17期1408-1412,共5页Zhejiang Medical Journal

基　　金：国家自然科学基金自助项目(81673755)

摘　　要：目的探讨桔梗皂甙D(platycodin,PD)与伊马替尼(imatinib,IM)联合用药抑制慢性粒细胞白血病细胞株K562的作用及机制研究。方法体外培养CML细胞株K562,CCK-8测定PD和IM单药及联合用药对K562细胞增殖的抑制作用;流式细胞仪检测Annexin V/PI标记的细胞凋亡率,Western blot方法检测cleaved caspase-3、cleaved caspase-9、PARP、cleaved PARP、Bcr/abl、p-AKT、p-m TOR蛋白表达。结果联合用药组对K562细胞的增殖抑制作用和诱导细胞凋亡率较单独用药组效果明显,差异均有统计学意义(均P<0.01)。与单药组比较,联合用药组可以明显上调cleaved caspase-3、cleaved caspase-9、cleaved PARP蛋白表达,同时下调PARP、Bcr/abl、p-AKT、p-m TOR蛋白的表达,差异均有统计学意义(P<0.01或0.05)。结论 PD与IM联合用药在抑制细胞增殖、诱导凋亡、抑制Bcr/abl蛋白和PI3K/AKT/m TOR信号通路方面明显优于单独用药。Objective To investigate the effect and mechanism of Platycodin （PD） combined with imatinib （IM） on chronic myelogenous leukemia K562 cells in vitro.Methods Cultured K562 cells were treated with PD and imatinib alone or in combination.Cell proliferation was examined by CCK8 assay.Cell apoptosis were detected by Annexin V FITC/PI double staining.The change of mitochondrial trans-membrane potential was measured by JC-1 staining.The protein expression of cleaved caspase-3,cleaved caspase-9,PARP,cleaved PARP,Bcr/abl,p-AKT and p-mTOR were detected by Western blot.Results The inhibitory effects of PD combined with imatinib on proliferation and apoptosis of K562 cells were significantly higher than those of the control group or single drug groups （all P〈0.01）.The expression of cleaved caspase-3,cleaved caspase-9 and cleaved PARP proteins was significantly up-regulated in the combination group,and the expression of PARP,Bcr/abl,p-AKT and p-mTOR proteins was significantly down-regulated （P〈0.01 or 0.05）.Conclusion Platycodin D combined with imatinib can significantly increase the inhibitory effect on cell proliferation and induce apoptosis of K562 cells compared with single drugs,which may be related to Bcr/abl protein and PI3K/AKT/mTOR signaling pathway.

关 键 词：梗皂甙D 伊马替尼 K562 BCR/ABL融合基因 PI3K//AKT/mTOR信号途径 

分 类 号：R733.72[医药卫生—肿瘤]