摘要
目的探讨二甲双胍联合环氧化酶-2(COX-2)选择性抑制剂塞来昔布对胃癌SGC-7901细胞增殖凋亡的影响及其机制。方法以不同浓度的二甲双胍和塞来昔布处理体外培养的SGC-7901细胞,MTT法检测细胞的存活率。联合实验分为:对照组(未加药)、二甲双胍组(加入浓度为10 mmol/L二甲双胍)、塞来昔布组(加入浓度为100μmol/L塞来昔布)和联合组(加入浓度为10 mmol/L二甲双胍和100μmol/L塞来昔布),药物作用72 h后,采用MTT法检测细胞的存活率,流式细胞仪检测细胞的周期变化和凋亡率,Western blotting检测PCNA、Cyclin D1、Bax和Bcl-2蛋白的表达。结果二甲双胍和塞来昔布均能够呈时间-剂量依赖性抑制SGC-7901细胞增殖。与对照组相比,各加药组细胞的存活率均明显降低(P<0.05),且联合组细胞的存活率明显低于二甲双胍和塞来昔布单药处理组(P<0.05)。二甲双胍和塞来昔布均可使SGC-7901细胞在G_0/G_1期所占百分比增加,S期百分比减少(P<0.05),但二甲双胍对G_2期细胞无明显影响(P>0.05),而塞来昔布可使G_2期细胞所占百分比降低(P<0.05);两药联用可增强单药处理组对G_0/G_1期的阻滞(P<0.05)。二甲双胍和塞来昔布单药处理组细胞的凋亡率明显高于对照组(P<0.05),联合用药后细胞的凋亡率明显高于单药处理组(P<0.05)。二甲双胍和塞来昔布均能使SGC-7901细胞中PCNA、Cyclin D1和Bcl-2表达降低,而Bax表达升高(P<0.05);联合用药后,细胞中PCNA、Cyclin D1、Bax和Bcl-2的表达变化明显高于二甲双胍和塞来昔布的单药作用(P<0.05)。结论二甲双胍和COX-2选择性抑制剂塞来昔布联合作用可协同抑制胃癌SGC-7901细胞增殖,促进细胞凋亡,其作用机制可能与下调PCNA、Cyclin D1、Bcl-2和上调Bax表达有关。
Objective To investigate the effect of Metformin combined with cyclooxyenase 2(COX-2)selective inhibitor Celecoxib on proliferation and apoptosis of gastric cancer SGC-7901 cells and its mechanism.Methods SGC-7901 cells cultured in vitro were treated with different concentrations of Metformin and Celecoxib,and cell viability was detected by MTT assay.The combined experiment was divided into control group(untreated),Metformin group(10 mmol/L Metformin),Celecoxib group(100μmol/L Celecoxib)and the combined group(10 mmol/L Metformin and 100μmol/L Celecoxib).After drug treatment for 72 hours,the cell viability was detected by MTT,and the cell cycle change and the apoptosis rate were measured by flow cytometry,and the expressions of PCNA,Cyclin D1,Bax and Bcl-2 proteins in the cells were tested by Western blotting.Results The proliferation of SGC-7901 cells was both inhibited by Metformin and Celecoxib in a time-dose dependent manner.Compared with control group,the survival rate of the cells in each addition group was decreased significantly(P<0.05),and the survival rate of the combined group was significantly lower than the Metformin and the Celecoxib single drug treatment group(P<0.05).The percentage of SGC-7901 cells in the G 0/G 1 phase was increased,and the percentage of S phase was decreased by Metformin and Celecoxib(P<0.05),but there was no significant effect on G 2 cells by Metformin(P>0.05),and the percentage of G 2 cells could be reduced by Celecoxib(P<0.05).The effect of G 0/G 1 phase arrest in the single drug treatment group was increased by combined use of two drugs.The apoptosis rate of Metformin and Celecoxib treatment group was significantly higher than that of control group(P<0.05),and the apoptosis rate of the cells was significantly higher than that of single drug treatment group(P<0.05).The expressions of PCNA,Cyclin D1 and Bcl-2 in SGC-7901 cells were both reduced and the expression of Bax were both increased by Metformin and Celecoxib(P<0.05).After combined use of drugs,the expressions of PCNA,
作者
张永恒
常廷民
ZHANG Yongheng;CHANG Tingmin(Department of Pharmacy,the First Affiliated Hospital of Xinxiang Medical University,Xinxiang 453100,China;Department of Gastroenterology,the First Affiliated Hospital of Xinxiang Medical University,Xinxiang 453100,China)
出处
《胃肠病学和肝病学杂志》
CAS
2019年第4期429-433,438,共6页
Chinese Journal of Gastroenterology and Hepatology
