E2F1对前列腺癌的细胞周期与凋亡的调控

The regulation role of E2F1 in cell cycle and apoptosis of prostate cancer

目的探讨E2F1转录因子对前列腺癌细胞的细胞周期及凋亡的影响。方法从高通量基因芯片结果中获得前列腺癌相关差异表达基因E2F1,进一步通过E2F1抑制及过表达质粒转染前列腺癌细胞,运用流式细胞技术检测转染后前列腺癌细胞的细胞周期及细胞凋亡变化。结果DU145/LNCa P转染质粒后,对照于空白组,转染si E2F1的细胞株,E2F1表达量明显下降(DU145:抑制率=77.30%,P<0.01;LNCa P:抑制率=79.89%,P<0.01);转染了Hi-E2F1的细胞株,E2F1表达量明显升高(DU145:倍数=8681,P<0.01;LNCa P:倍数=14424,P<0.01)。细胞周期实验结果显示,与空白组对比,抑制E2F1表达后的DU145及LNCa P细胞株细胞周期明显被抑制(P<0.05);高表达E2F1的LNCa P细胞株的细胞周期缩短(P<0.05),而在DU145细胞株中无明显差异。细胞凋亡实验发现,抑制E2F1表达后的DU145和LNCa P细胞株细胞凋亡明显增加(DU145 P<0.01;LNCa P P<0.05);相反,高表达E2F1后,细胞凋亡明显减少(P<0.05)。结论 E2F1可使前列腺癌细胞的细胞周期缩短,并抑制前列腺癌细胞凋亡,这说明E2F1在前列腺中确实起着促癌的作用。

Objective To investigate the effect of E2F1 transcription factor on cell cycle and apoptosis of prostate cancer cell lines. Methods The different expression gene, E2F1, which related to prostate cancer from high-throughput microarray was obtained. Furthermore, the cell cycle and apoptosis of prostate cancer cells were detected by flow cytometry after transfection with E2F1 inhibitor and overexpression plasmid. Results After DU145/ LNCa P transfection, E2F1 expression levels compared to the control groups, the data showed the expression of E2F1 was significantly decreased in the groups of si E2F1 cell lines（DU145, the inhibition rate =77.30% P〈0.01; LNCa P, the inhibition rate=79.89%, P〈0.01）; While the expression of E2F1 was significantly increased in the overexpression groups（DU145, P〈0.01, fold=8681; LNCa P, fold=14424, P〈0.01）. The results of cell cycle analysis showed that after inhibition of the expression of E2F1 caused cell cycle arrest at the G0/G1 phase（P〈0.05）; On the contrary, a higher proportion of S, G2/M phase was shown in the over-expression-E2F1 LNCa P cell lines（P〈0.05）. Lastly, the cell apoptosis of DU145 and LNCa P cells was significantly increased after the inhibition of E2F1 expression（DU145, P〈0.01; LNCa P, P〈0.05） while an opposite result shown in the E2F1 overexpression cell lines（P〈0.05）. Conclusion E2F1 can shorten the cell cycle and inhibit apoptosis of prostate cancer cells, which indicates that E2F1 can sever as a tumor promoter in prostate cancer.