肿瘤错配修复基因PMS2及活化Akt1在不同卵巢癌细胞株中的表达及相关性

The expression and the relativity of PMS2 and P-Akt S473 in different human ovarian cancer cell lines

目的检测Akt1、P-Akt S473和PMS2蛋白在人类不同卵巢癌细胞株(A2780、Caov3、C13*和ES2)中的表达水平及相关性。方法应用Western blot检测Akt1、P-Akt S473和PMS2蛋白分别于A2780、Caov3、C13*和ES2细胞中表达水平;应用Akt1激动剂胰岛素样生长因子-1(IGF-1)及Akt1特异性抑制剂API-2调节Akt1活化水平,观察PMS2蛋白表达水平变化。结果 Akt1,P-Akt S473及PMS2 3种蛋白在A2780,Caov3,C13*和ES2卵巢癌细胞内均表达,但表达水平高低不一,即Akt1的活化形式P-Akt S473与PMS2蛋白表达呈负相关;应用IGF-1上调Akt1的活性后,ES2和Caov3中PMS2表达水平明显下降,且与IGF-1的作用存在时间依赖性;应用特异性抑制剂API-2抑制Akt1的活性后,A2780中PMS2表达水平明显升高,且与API-2的作用存在时间依赖性。结论人类卵巢癌细胞中PMS2蛋白的表达水平可能受活化Akt1的直接调控。

Objective To evaluate the expression and the relativity of PMS2,Akt1 and P-Akt S473 protein in A2780,Caov3,C13＊and ES2 ovarian cancer cell lines.Methods The expression of PMS2,Akt1 and P-Akt S473 protein in A2780,Caov3,C13＊and ES2 ovarian cancer cells was detected by Western Blot.After treated with IGF-1（Akt1activator）and API-2（specific Akt1inhibitor）,Caov3,ES2 and A2780cells were collected and the level of PMS2 was detected by Western Blot.Results PMS2,Akt1 and P-Akt S473 proteins were detected in all of the four ovarian cancer cell lines with varied expression levels,and the activity of Akt1 was inversely related to PMS2 expression in ovarian cancer cells.Exposed to Akt kinase stimulator IGF-1,ES2 and Caov3cells were detected with a dramatically PMS2 decreasing.Meanwhile,the decreasing of PMS2 protein was time-dependent on IGF-1.Treated with API-2,Akt kinase specific inhibitor,A2780 was detected with PMS2 dramatically increasing,and the increasing of PMS2 protein was time-dependent on API-2.Conclusion In ovarian cancer cells,PMS2 expression could be directly regulated by activated Akt1.