The Effect Of Inhibiting FKBP5on The Growth Of Prostate Cancer Cell Lines And Nude Mice Xenograft

Objective:Detection the expression of FKBP5in the human tissues of benign prostatic hyperplasia, androgen-dependent prostate cancer, prostate cancer after androgen deprivation therapy and castrate-resistant prostate cancer, to explore the mechanism of FKBP5in the course of androgen-dependent prostate cancer transformed to castrate-resistant prostate cancer. Observation the effect of knockdowning or inhibiting FKBP5gene for the growth of prostate cancer cell and mice xenograft. Attempting to build a xenograft prostate cancer mouse model from human prostate cancer tissue.Methods:Immunohistochemistry and Western Blot methods were used to detect the protein expression of FKBP5in the human tissues of benign prostatic hyperplasia, androgen-dependent prostate cancer, prostate cancer after androgen deprivation therapy and castrate-resistant prostate cancer. The proliferative activity of these cells were detected by MTT assay and cell counting, after the prostate cance LNCaP and C4-2cells treated by ShRNA and FK506. Establishing prostate cancer nude mice with subcutaneous xenografts grown from implanted LNCaP cells, the growth curves and weight of tumors were recorded after these mice were treated ShRNA and FK506. Then the expression of FKBP5and BRDU were detected by Immunohistochemistry. Building a xenograft prostate cancer model in subrenal capsule of NOD-Scid mouse supplemented androgen from human prostate cancer tissue.Results:1. The expression of FKBP5protein in the human tissues:1) FKBP5protein expression in the human androgen-dependent prostate cancer(ADPC) tissues was higher than benign prostate hyperplasia(BPH) tissues. And there was significant difference (P<0.05).2) FKBP5protein expression in the androgen-dependent prostate cancer(ADPC) tissues was higher than androgen deprivation therapy prostate(ADT) cancer tissues. And there was significant difference (P<0.05).3) FKBP5protein expression in the androgen-dependent prostate cancer tissues was lower than castrate-resistant prostate cancer(CRPC) tissues. And there was significant difference (P<0.05). 2. The effect of knockdowning or inhibiting FKBP5on the growth of prostate cancer cell lines and nude mice tumor:1)Cytological experiments:The proliferative activity of the prostate cance LNCaP and C4-2cells were decreased significantly compared with control groups after the FKBP5were knockouted or inhibited by ShRNA and FK506by MTT assay and cell counting And there was significant difference (P<0.05).2)Animal experiments:The size and weight of tumors from treated groups were significantly less than that in control groups after the FKBP5were knockouted or inhibited by ShRNA and FK506.And there was significant difference (P<0.05).3.The prostate cancer mouse model:Human prostate cancer tissue were planted in the subrenal capsule of NOD-SCID mice supplemented androgen, the xenografts were alive and can be transplanted to other NOD-scid mice.Conclusions:1. The expression of FKBP5protein in the human androgen-dependent prostate cancer tissues was higher than benign prostate hyperplasia tissues. The expression of FKBP5protein in the androgen-dependent prostate cancer tissues was higher than androgen deprivation therapy prostate cancer tissues. The expression of FKBP5protein in the androgen-dependent prostate cancer tissues was lower than castrate-resistant prostate cancer tissues. FKBP5may play a important role in the progression of the prostate cancer.2. The growth of prostate cancer cell lines and xenografts in nude mice can be inhibited by knockouting or inhibiting FKBP5, so FKBP5may be one of therapeutic targets of prostate cancer, especially castrate-resistan prostate cancer.3. The prostate cancer mouse model:Human prostate cancer tissue were planted in the subrenal capsule of NOD-SCID mice supplemented androgen, the xenografts were alive and can be transplanted to other NOD-scid mice. This provides a new animal experiment platform for the research of prostate cancer.