奥沙利铂对肝癌细胞HepG2细胞周期的影响  

Effect of Oxaliplatin on cell cycle of hepatocellular carcinoma cell line HepG_2

作　　者：高洁[1] 汪蕊[2] 杨清玲[3,4] 陈昌杰[3,4] 吴穷[2] 

机构地区：[1]蚌埠医学院第一附属医院检验科,安徽蚌埠233000 [2]蚌埠医学院第一附属医院肿瘤内科,安徽蚌埠233000 [3]蚌埠医学院第一附属医院 [4]蚌埠医学院生化教研室,安徽蚌埠233000

出　　处：《浙江大学学报（医学版）》2013年第4期437-442,460,共7页Journal of Zhejiang University(Medical Sciences)

基　　金：安徽省自然科学基金项目(1208085MH170)

摘　　要：目的:探讨奥沙利铂(Oxaliplatin,L-OHP)对人肝癌细胞株HepG2周期的影响及其相关机制,为其应用于原发性肝细胞癌临床治疗提供理论依据。方法:MTT方法检测L-OHP对肝癌细胞HepG2生长的抑制作用;流式细胞术(FCM)检测L-OHP诱导HepG2细胞周期阻滞的作用;RTPCR和Western blot方法观察L-OHP对细胞周期调节因子CyclinD1、CDK2、CDK4及p16、p21、p53表达的影响。结果:MTT结果显示L-OHP对HepG2细胞增殖抑制率随药物浓度增加及作用时间延长有升高趋势,呈时间剂量依赖性。L-OHP能够诱导HepG2细胞周期阻滞于S期,并可下调CDK4和CyclinD1蛋白的表达,上调p21,p53蛋白的表达,CDK2和p16表达无明显变化。结论:L-OHP可能通过影响CDK4、CyclinD1及p21的活性使HepG2细胞阻滞在S期,从而抑制肝癌细胞HepG2的增殖。Objective： To investigate the effect of Oxaliplatin （L-OHP）on cell cycle in hepatoeellular carcinoma cell line HepG2 and the involved mechanism. Methods： Inhibitory effect of L-OHP on the proliferation of HepG2 cells was determined by MTF assay. Cell cycle distribution was shown by flow FCM. The expression levels of cyclinD1 , CDK2, CDK4, p16, p21, p53 were detected by RT-PCR and Western blot. Results： MTT method revealed that L-OHP inhibited proliferation of hepatocellular carcinoma HepG2 cells in a dose- and time-dependent manner. L-OHP induced S cell cycle arrest in HepG2 cell; down-regulated the levels of CDK4, cyelinDi and up-regulated the levels of p21, p53. There were no significant changes of CDK2 and p16 after L-OHP treatment. Conclusions： L-OHP inhibits the proliferation of HepGz cells by blocking cell at S stage, which may be resulted from the activity of CDK4, CyclinD1 and p21.

关 键 词：肝肿瘤 药物疗法 细胞周期 药物作用 铂化合物 药理学 流式细胞术 印迹法 蛋白质 方法 肿瘤细胞 培养的 奥沙利铂 肝癌 

分 类 号：R735.7[医药卫生—肿瘤]