MAPK信号转导通路在托瑞米芬非雌激素抗肿瘤中的作用

目的探讨托瑞米芬(TOR)对乳腺癌细胞株MCF7的非雌激素抗肿瘤作用及促分裂原激活蛋白激酶(MAPK)信号转导通路在其中所发挥的作用。方法采用SRB法测量TOR单独或联合MEK抑制剂PD98059对乳腺癌细胞株MCF7活性的抑制;Western blotting检测不同浓度TOR对MCF7细胞株磷酸化ERK的影响。结果TOR抑制乳腺癌细胞株MCF7的活性,抑制强度呈浓度依赖性。PD98059与TOR联用,可显著增强TOR对MCF7细胞株的细胞毒作用,对细胞株抑制率大于两药单独应用之和。5、10、20μmol/L的TOR对MCF7细胞株中磷酸化ERK有明显的浓度依赖性抑制作用。结论MAPK信号转导通路在TOR非雌激素抗肿瘤中发挥重要作用,MAPK通路抑制剂与TOR联合应用可发挥协同作用,增强其抗肿瘤效用。

Mitogen-activated protein kinase pathway in antitumor effect of toremifene

Objective To study the antitumor effect of toremifene on MCF7 cell lines,and investigate the role of mitogen-activated protein kinase pathway. Methods Inhibitory effect of toremifene alone or combined with MEK inhibitor PD98059 on MCF7 cells was measured by SRB test,and that on phosphorylated ERK was detected by Western blotting.Results Toremifene exhibited a concentration-dependent inhibitory effect on the activity of MCF7 cells.Phosphorylated ERK was significantly inhibited by 5,10 and 20 mmol/L toremifene.Combined with PD98059,toremifene had a significantly enhanced cytotoxity effect,which exceeded that of application alone. Conclusion Mitogen-activated protein kinase pathway may play an important role in the antitumor effect of toremifene which is independent of estrogens.Combined with PD98059,the antitumor effect of toremifene can be reinforced,indicating a synergistic effect of these two drugs.