Preliminary study on the effect and mechanism of FKBP5 on prostate cancer C4-2 cells
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摘要: 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。Abstract: 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.
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Key words:
- prostate cance /
- FKBP5 /
- FK506 /
- NF-κB
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