环氧化酶-2反义RNA联合塞莱昔布对肝癌细胞增殖和凋亡的影响  

Effect of cyclooxygenase-2 antisense RNA combined with celecoxib on the proliferation and apoptosis of hepatoma cells

作　　者：朱跃坤[1] 赵宪琪[1] 汪大伟 张伟[1] 田茂霖[1] 李正天[1] 赵龙[1] 李超[1] 姜洪池[1] ZHU Yuekun;ZHAO Xianqi;WANG Dawei(Department of General Surgery,The First Affiliated Hospital of Harbin Medical University,Harbin 150001,China)

机构地区：[1]哈尔滨医科大学附属第一医院普外科,哈尔滨150001

出　　处：《临床肝胆病杂志》2018年第12期2614-2618,共5页Journal of Clinical Hepatology

基　　金：黑龙江省青年科学基金(QC2009C17);黑龙江省教育厅科学技术研究基金(11541201)

摘　　要：目的研究环氧化酶-2(COX-2)反义RNA与塞来昔布联合应用对肝癌细胞(CBRH7919)的抗肿瘤作用。方法观察塞莱昔布对肝癌细胞株CBRH7919、CBRH7919-E及CBRH7919-A(转染反义COX-2基因片段组)体外抗增殖活性、细胞周期及凋亡的影响。通过MTT法、细胞周期分析、RT-PCR等方法测定肝癌细胞株体外增殖的变化。计量资料多组间比较采用多因素方差分析,进一步两两比较采用SNK-q检验。结果加入塞来昔布作用各组细胞后,CBRH7919-A细胞较CBRH7919和CBRH7919-E细胞生长速度明显减慢(F=38. 303,P <0. 01),且对塞来昔布具有时间、剂量依赖性(F值分别为162. 638、22. 666,P值均<0. 01)。塞莱昔布能够明显提高G0/G1比例,对S期细胞有显著的抑制作用,且具有剂量依赖性(F=32. 515,P <0. 01),而G2/M变化不明显。CBRH7919-A细胞较CBRH7919,CBRH7919-E细胞对塞来昔布作用更敏感(F=1219. 506,P <0. 01)。加入不同浓度的塞来昔布后(40、80μmol/L),3组细胞凋亡均明显增加(P值均<0. 01); CBRH7919-A与CBRH7919、CBRH7919-E 3组间凋亡差异无统计学意义(P> 0. 05)。结论 COX-2反义RNA及塞来昔布可协同抑制肝癌细胞(CBRH7919)的体外生长增殖,抑制细胞周期,对促进肝癌细胞凋亡有潜在的治疗作用。Objective To investigate the antitumor effect of cyclooxygenase-2(COX-2)antisense RNA combined with celecoxib on hepatoma CBRH7919 cells.Methods The effect of celecoxib on in vitro proliferative activity,cell cycle,and apoptosis of hepatoma cell lines CBRH7919,CBRH7919-E,and CBRH7919-A(transfected with COX-2 antisense gene segment)were observed.MTT assay,cell cycle analysis,and RT-PCR were used to evaluate the change in in vitro proliferation of hepatoma cell lines.A multivariate analysis of variance was used for comparison of continuous data between groups,and the SNK-q test was used for further comparison between two groups.Results After the treatment with celecoxib,CBRH7919-A cells had a significant reduction in growth rate compared with CBRH7919 and CBRH7919-E cells(F=38.303,P<0.01),in a time-and dose-dependent manner(F=162.638 and 22.666,both P<0.01).Celecoxib significantly increased the proportion of cells in G0/G1 phase and had a marked inhibitory effect on cells in S phase in a dose-dependent manner(F=32.515,P<0.01),while there was no significant change in the proportion of cells in G2/M phase.Compared with CBRH7919 and CBRH7919-E cells,CBRH7919-A cells were more sensitive to celecoxib(F=1219.506,P<0.01).After the treatment with celecoxib at different concentrations(40 and 80μmol/L),all three groups had a significant increase in cell apoptosis(all P<0.01),and there was no significant difference in apoptosis between the three groups(P>0.05).Conclusion COX-2 antisense RNA combined with celecoxib can inhibit the in vitro growth and proliferation and cell cycle of hepatoma CBRH7919 cells,promote apoptosis,and thus exert a potential therapeutic effect on hepatoma cells.

关 键 词：癌 肝细胞 环氧化酶2 环氧化酶2抑制剂 细胞增殖 细胞凋亡 

分 类 号：R735.7[医药卫生—肿瘤]