【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.更多还原

【Abstract】 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.更多还原