FKBP5对前列腺癌C4-2细胞生长的影响及机制的初步研究

Preliminary study on the effect and mechanism of FKBP5 on prostate cancer C4-2 cells

目的:观察抑制FK506结合蛋白5(FKBP5)基因表达和应用FKBP5的抑制剂FK506对前列腺癌细胞生长的影响,并初步探究其作用机制。方法:利用shRNA和FK506处理前列腺癌C4-2细胞,然后用MTT法检测细胞生长变化情况;通过Western blot检测处理过的C4-2细胞中NF-κB信号通路中相关蛋白的变化。结果:利用shRNA和FK506抑制C4-2细胞中的FKBP5的表达后,MTT法显示实验组细胞的增殖活性明显低于对照组(P<0.05),FK506对细胞生长有明显的抑制作用,并且这种作用具有浓度依赖性。在C4-2细胞系中,降表达FKBP5后发现IκBα表达量增高,磷酸化的NF-κB表达升高,并且胞浆的NF-κB含量增多而细胞核中的NF-κB明显减少。结论:抑制FKBP5的表达可以抑制前列腺癌C4-2细胞系的生长,FKBP5的抑制剂FK506同样可以抑制细胞生长,FKBP5对细胞生长的影响可能是通过调节NF-κB信号通路来实现的,而FKBP5可能是去势抵抗性前列腺癌的一个新的治疗靶点。

Objective：To observe the effect of inhibiting the FKBP5 gene on the growth of prostate cancer cells and explore the mechanism.Method：The growth activity of these cells were detected by MTT assay,after the C4-2 cells were treated by shRNA and FK506.We detected the proteins content change involved in the NF-κB signaling pathway by Western blot.Result：After the expression of FKBP5 was decreased by shRNA or the FKBP5 was inhibited by FK506,the growth of the prostate cancer C4-2 cell decreased significantly compared with the control group by MTT assay（P〈0.05）.The inhibition of FK506 for the cell growth had the concentration dependence.In C4-2 cells,we found that the expression of IκBαand the phosphorylated NF-κB increased,after knockout of the FKBP5.Moreover the content of NF-κB in the cytoplasm increased and the NF-κB in the cell nucleus decreased.Conclusion：The growth of C4-2 cell can be inhibited by knockout of FKBP5 and FK506.The effect of FKBP5 on cell growth may involve the NF-κB pathway.FKBP5 may be a new therapeutic target for prostate cancer.