高三尖杉酯碱通过抑制ERK1/2信号通路逆转卵巢癌细胞顺铂耐药的研究  

Homharringtonine reverses cisplatin resistance in ovarian cancer cells by inhibiting ERK1/2 signaling pathway

作　　者：程琛[1] 杨建 秦公照 具晟 CHENG Chen;YANG Jian;QIN Gong-zhao;JU Sheng(Department of Gynecology,Suzhou Hospital Affiliated to Nanjing Medical University,Suzhou 215002;Department of Thoracic Surgery,the First Affiliated Hospital of Suzhou University,Suzhou 215001,Jiangsu,China)

机构地区：[1]南京医科大学附属苏州医院妇科,江苏苏州215002 [2]苏州大学附属第一医院胸外科,江苏苏州215001

出　　处：《川北医学院学报》2022年第12期1519-1523,共5页Journal of North Sichuan Medical College

基　　金：江苏省苏州市民生科技计划项目(SYS2020174)。

摘　　要：目的:探讨高三尖杉酯碱(HHT)逆转卵巢癌细胞顺铂(DDP)耐药的机制。方法:将DDP耐药卵巢癌细胞A2780/DPP分成对照组、DDP组、HHT组、联合组(DDP+HTT)、ERK1/2抑制剂组(PD98059)、DDP+ERK1/2抑制剂组(DDP+PD98059)、ERK1/2激活剂组(ISO)、联合+ERK1/2激活剂组(DDP+HTT+ISO)。采用CCK-8实验检测细胞增殖,流式细胞术检测细胞凋亡,Western blot检测Bax、Bcl-2、ERK1/2、p-ERK1/2蛋白表达。结果:与对照组比较,联合组卵巢癌细胞A2780/DPP存活率降低,凋亡率和Bax蛋白表达增多,Bcl-2、p-ERK1/2/ERK1/2蛋白表达减少,差异有统计学意义(P<0.05);DDP和HTT组卵巢癌细胞A2780/DPP存活率、凋亡率和Bax、Bcl-2、p-ERK1/2/ERK1/2蛋白表达水平比较,差异无统计学意义(P>0.05)。与对照组、DDP组、ERK1/2抑制剂组比较,DDP+ERK1/2抑制剂组p-ERK1/2/ERK1/2蛋白表达减少,存活率降低,凋亡率和Bax蛋白表达增多,Bcl-2蛋白表达减少,差异有统计学意义(P<0.05)。与对照组比较,ERK1/2激活剂组p-ERK1/2/ERK1/2蛋白表达增多,存活率升高,凋亡率和Bax蛋白表达减少,Bcl-2蛋白表达增多,差异有统计学意义(P<0.05)。与联合组比较,联合+ERK1/2激活剂组卵巢癌细胞A2780/DPP中p-ERK1/2 ERK1/2蛋白表达增多,存活率升高,凋亡率和Bax蛋白表达减少,Bcl-2蛋白表达增多,差异有统计学意义(P<0.05)。结论:高三尖杉酯碱可能通过抑制ERK1/2信号通路逆转卵巢癌细胞DDP耐药。Objective:To study the mechanism of cisplatin(DDP)resistance in homoharringtonine(HHT)ovarian cancer cells.Methods:DDP-resistant ovarian cancer cells A2780/DPP were divided into control group,DDP group,HHT group,combined group(DDP+HTT),ERK1/2 inhibitor group(PD98059),DDP+ERK1/2 inhibitor group(DDP+PD98059),ERK1/2 activator group(ISO),and combined+ERK1/2 activator group(DDP+HTT+ISO).Proliferation was detected by CCK-8 assay,apoptosis was detected by flow cytometry,and protein expressions of Bax,Bcl-2,ERK1/2 and p-ERK1/2 were detected by Western blot.Results:Compared with the control group,the survival rate of ovarian cancer cells A2780/DPP in the combined group decreased,the apoptosis rate and Bax protein expression increased,and the protein expressions of Bcl-2 and p-ERK1/2/ERK1/2 decreased(P<0.05),but the survival rate,apoptosis rate and protein expression of Bax,Bcl-2,p-ERK1/2/ERK1/2 in ovarian cancer cells A2780/DPP in DDP and HTT groups did not change significantly.Compared with the control group,DDP group and ERK1/2 inhibitor group,the expression of p-ERK1/2/ERK1/2 protein in DDP+ERK1/2 inhibitor group decreased,the survival rate decreased,the apoptosis rate and Bax protein expression increased,Bcl-2 protein expression decreased(P<0.05).Compared with the control group,the expression of p-ERK1/2/ERK1/2 protein in the ERK1/2 activator group increased,the survival rate increased,the apoptosis rate and Bax protein expression decreased,and the Bcl-2 protein expression increased(P<0.05).Compared with the combined group,the expression of p-ERK1/2/ERK1/2 protein in ovarian cancer cells A2780/DPP in the combined+ERK1/2 activator group increased,the survival rate increased,the apoptosis rate and Bax protein expression decreased,and Bcl-2 protein expression increased(P<0.05).Conclusion:Homoharringtonine reverses DDP resistance of ovarian cancer cells by inhibiting ERK1/2 signaling pathway.

关 键 词：高三尖杉酯碱(HHT) 卵巢癌 顺铂(DDP)耐药 ERK1/2信号 

分 类 号：R737.31[医药卫生—肿瘤]