摘要
[目的]探讨PI3K/Akt信号通路抑制剂LY294002联合血红素加氧酶-1(HO-1)抑制剂Znpp IX对人乳腺癌MCF7/Adr细胞增殖及侵袭能力的影响.[方法]将Znpp IX(0.625~10.000μmol/L)与LY294002(5~80μmol/L)单独或联合应用于人乳腺癌MCF7/Adr细胞,用MTT法检测药物对MCF7/Adr细胞增殖的影响.实验分为对照组、LY294002组(10μmol/L)、Znpp IX组(1.250μmol/L)和联合用药组(LY294002 10μmol/L+Znpp IX1.250μmol/L),用Transwell小室测定各组MCF7/Adr细胞的侵袭力和迁移力,Western blot法检测Akt,p-Akt和HO-1蛋白的表达水平.[结果]联合用药组、LY294002组及Znpp IX组MCF7/Adr细胞的增殖抑制率分别为58.60%±3.24%,42.50%±2.44%和39.70%±3.21%,联合用药组MCF7/Adr细胞的增殖抑制率明显高于LY294002组和Znpp IX组(P<0.05).LY294002和Znpp IX单独或联合应用均可显著抑制人乳腺癌MCF7/Adr细胞的侵袭和转移(P<0.05),其中联合用药组抑制作用显著优于LY294002组和Znpp IX组(P<0.05).Western blot检测结果显示,各组Akt蛋白表达水平间差异无统计学意义(P>0.05);LY294002组p-Akt,HO-1表达水平均明显低于对照组(P<0.05),Znpp IX组HO-1表达水平明显低于对照组(P<0.05),与LY294002组和Znpp IX组比较,联合用药组p-Akt,HO-1水平均明显降低(P<0.05).[结论]Znpp IX和LY294002单独应用均可抑制人乳腺癌MCF7/Adr细胞的增殖、侵袭及转移,联合应用时作用加强,提示Znpp IX和LY294002联合应用具有协同增效作用.
OBJECTIVE To explore the effects of LY294002(an inhibitor of PI3 K/Akt signal pathway)combined with Znpp IX(an inhibitor of heme oxygenase-1)on proliferation and invasion of human breast cancer cell MCF7/Adr.METHODS The effects of Znpp IX(0.625~10.000μmol/L)and LY294002(5~80μmol/L)alone or combined on the proliferation of MCF7/Adr cells were detected by MTT.The cells were divided into four groups:the control group,LY294002 group(10μmol/L),Znpp IX group(1.250μmol/L)and the combination group(LY294002 10μmol/L + Znpp IX 1.250μmol/L).The invasion and migration of MCF7/Adr cells in each group were measured by Transwell chamber,and Western blot was used to detect the expressions of AKT,p-AKT and HO-1.RESULTS The inhibition rate of MCF7/Adr cells in the combination,LY294002 and Znpp IX group was58.6%±3.24%,42.50%±2.44% and 39.70%±3.21%respectively.The inhibition rate of the combination group was significantly higher than that of LY294002 and Znpp IX group(P〈0.05).Both alone and combined application of LY294002 and Znpp IX could significantly inhibit the invasion and metastasis of human breast cancer cell MCF7/Adr(P〈0.05),and the inhibitory effect of the combination group was significantly better than that of LY294002 group and Znpp IX group(P〈0.05).The results of western blot showed that there was no significant difference in the expression level of Akt between the groups(P〉0.05),while the expressions of p-Akt and HO-1 in LY294002 group were obviously lower than that in the control group(P〈0.05),and the expression of HO-1 in Znpp IX group was significantly lower than that in the control group(P〈0.05),as compared with LY294002 and Znpp IX group,the expressions of p-Akt and HO-1 in the combination group were obviously reduced(P〈0.05).CONCLUSIONZnpp IX and LY294002 could inhibit the proliferation,invasion and metastasis of human breast cancer MCF7/Adr cell line,and the effects were enhanced by combined application.It suggested that the combined application of Znpp IX and LY294002 had synergistic effect.
作者
朴丽花
韩龙哲
张默函
姜京植
蔡英兰
金政
金雪梅
PIAO Lihua;HAN Longzhe;ZHANG Mohan;JIANG Jingzhi;CAI Yinglan;JIN Zheng;JIN Xuemei(Department of Anatomy and Histology and Embryology,Yanbian University College of Medicine;Department of Pathology,Affiliated Hospital of Yanbian University,Yanji 133002,Jilin,China)
出处
《延边大学医学学报》
CAS
2018年第2期94-97,共4页
Journal of Medical Science Yanbian University
基金
吉林省教育厅资助项目
吉教科合字2015第19号
吉林省延边大学博士科研启动基金项目(No.950010003)