The Study Of The Role And Mechanism Of FKBP5 In Prostate Cancer Cell Lines

Objective:Detect the expression of FKBP5 in prostate cancer cell lines,observe the effect of knockdowning or inhibiting FKBP5 gene for the growth of prostate cancer cell and explore the mechanism of FKBP5 in the course of androgen dependent prostate cancer transformed to castrate resistant prostate cancer.Preliminarily imagine the clinical significance of FKBP5 for the treatment the androgen independence prostate cancer.Methods:Western Blot methods was used to detect the protein expression of FKBP5 in several prostate cancer cell lines;The growth activity of these cells were detected by MTT assay,after the LNCaP and C4-2 cells were treated by ShRNA and FK506;Detect the protein changes involved in the NF-?B signaling pathway by western blot,after the C4-2 cells were treated by ShRNA and FK506.Results:1.The expression of FKBP5 is high in the prostate cancer cell lines(C4-2?LNCaP?PC3?DU 145).The expression of FKBP5 in PC3 and DU 145 which have no AR is higher than it in C4-2 and LNCaP which have AR;the expression of FKBP5 in androgen dependent cell line(LNCaP)is lower than it in castration resistant cell lines(C4-2,PC3,DU145).2.The proliferative activity of the prostate cancer LNCaP and C4-2 cells were decreased significantly compared with control groups after the FKBP5 were knockout or inhibited by ShRNA and FK506 by MTT assay(P<0.05).The inhibition of FK506 for the cells growth has the concentration dependence.3.In C4-2 cell lines,we found that the expression of I?B? increase,the expression of phosphorylated NF-?B increase,after knockout the FKBP5.Moreover the content of NF-?B in the cytoplasm increased and the NF-?B in the cell nucleus decreased significantly,which affects its role of transcription.4.In C4-2 cells,treated with different concentrations of FK506,the expression of IkB? and caspase-3 were increase with the increase of concentration of FK506.Conclusion:The expression of FKBP5 protein in the human androgen-dependent prostate cancer tissues was higher than benign prostate hyperplasia tissues.The expression of FKBP5 protein in the androgen-dependent prostate cancer tissues was higher than androgen deprivation therapy prostate cancer tissues.The expression of FKBP5 protein in the androgen-dependent prostate cancer tissues was lower than castrate-resistant prostate cancer tissues.FKBP5 may play a important role in the progression of the prostate cancer.In the four types of prostate cancer cell lines,the expression of FKBP5 is high and the growth of C4-2 and LNCaP cells can be inhibited by knockouting or inhibiting FKBP5,so FKBP5 may be one of therapeutic targets of prostate cancer,especially castrate resistant prostate cancer.The effect of FKBP5 on cell growth may be involved the NF-KB pathway.In a word,FKBP5 is a very potential molecular biomarkers and new treatament target in prostate cancer.