奥沙利铂通过p53信号通路抑制肝癌细胞增殖的机制研究  

The mechanism of oxaliplatin inhibits proliferation of hepatocellular carcinoma cell through p53 signaling pathway

作　　者：高洁[1] 丁淑琴[1] 邓蓉[1] 郭普[1] 张伦军[1] 黄桦 GAO Jie;DING Shu-qin;DENG Rong;GUO Pu;ZHANG Lun-jun;HUANG Hua(Department of Laboratory Medicine,The First Affiliated Hospital of Bengbu Medical College,Bengbu Anhui 233004;Department of Medical Laboratory,Bengbu Medical College,BengBu Anhui 233030,China)

机构地区：[1]蚌埠医学院第一附属医院检验科,安徽蚌埠233004 [2]蚌埠医学院医学检验系,安徽蚌埠233030

出　　处：《蚌埠医学院学报》2018年第8期984-988,共5页Journal of Bengbu Medical College

基　　金：蚌埠医学院科研课题(byky1362;byky1730);安徽省高等学校自然科学研究项目(KJ2015B035by)

摘　　要：目的:研究奥沙利铂(L-OHP)对突变型肝癌细胞HuH-7、野生型肝癌细胞HepG2增殖与凋亡的影响,探讨p53信号通路相关蛋白在其中的作用。方法:MTT法检测L-OHP对HuH-7、HepG2细胞增殖的抑制效应;倒置显微镜观察L-OHP作用后2种细胞株形态的变化;流式细胞术检测L-OHP作用后细胞周期分布;Western blot法检测p53信号通路相关蛋白表达变化。结果:L-OHP能抑制HuH-7、HepG2细胞增殖,具有时间浓度依赖性(P<0.01);L-OHP作用后,可观察到细胞形态发生改变,细胞变圆、脱壁;L-OHP能够诱导HuH-7、HepG2细胞阻滞在细胞周期的S期,S期细胞的比例随L-OHP作用浓度增加而明显增加(P<0.01);L-OHP可激活p53信号通路,L-OHP改变2种细胞中p21、Bax、Bcl-2、p53、磷酸化p53(p-p53)蛋白表达(P<0.05),但对HuH-7细胞p-p53的表达无明显影响。结论:L-OHP可通过激活p53信号通路诱导肝癌细胞凋亡,其机制可能与调控p53通路相关蛋白p53、p-p53、p21、Bax、Bcl-2的表达有关。Objective： To investigate the effects of oxaliplatin（ L-OHP） on the proliferation and apoptosis of mutant type hepatocellular carcinoma cell line HuH-7 and wild type hepatocellular carcinoma cell line HepG2,and the role of p53 signaling pathway-related protein. Methods： The inhibiting effects of L-OHP on the proliferation of HuH-7 and HepG2 cells were detected using MTT assay. After HuH-7 and HepG2 cells were treated with L-OHP,the morphology changes of two cell lines were observed by inverted microscope,the cell cycle distribution was measured by flow cytometry,and the expression of p53 signaling pathway-related protein was detected using Western blot. Results： L-OHP could inhibit the proliferation of HuH-7 and HepG2 cells,which showed the concentration and timedependent manner（ P〈0. 01）. After treatment with L-OHP,the cells became round,off the wall and apoptosis. L-OHP could induce the HuH-7 and HepG2 cells stasising at S phase of cell cycle,and the proportion of cells increased with the increasing the concentration of L-OHP（ P〈0. 01）. L-OHP could activate the p53 signaling pathway,and regulate the protein expression levels of p21,Bax,Bcl-2 and p53 in HuH-7 and HepG2 cells（ P〈0. 05）,but the expression change of p-p53 in HuH-7 cells was not obvious. Conclusions： L-OHP can induce the apoptosis of hepatocellular carcinoma cells by activating the p53 signaling pathway,the mechanism of which may be related to regulating the expression of p53,p-p53,p21,Bax and Bcl-2 in p53 signaling pathway.

关 键 词：肝肿瘤 奥沙利铂 细胞周期 p53信号通路 

分 类 号：R735.7[医药卫生—肿瘤]