Androgen deprivation therapy has no effect on Pim-1 expression in a mouse model of prostate cancer

摘要

The aim of the present study was to observe the dynamic changes of proto-oncogene, serine/threonine kinase, Pim-1 at the gene and protein level in a mouse model of prostate cancer following surgical castration. Using LNCaP cells to establish a subcutaneous xenograft model and orthotopic prostate cancer BALB/c nude mouse models, the xenograft models were divided into an androgen-dependent prostate cancer group (ADPC), an androgen deprivation therapy (ADT) group and an androgen independent prostate cancer (AIPC) group. Reverse transcription-polymerase chain reaction (RT-PCR), RT-quantitative PCR, ELISA and immunohistochemistry analyses were performed to compare the expression levels of Pim-1, prostate-specific antigen (PSA) and androgen receptor (AR) in tumor tissue of three subgroups. Agarose gel electrophoresis revealed that the RT-PCR results of the ADPC (0.59±0.01) and AIPC groups (1.14±0.015) were significantly different when compared with the ADT group (0.62±0.026; P<0.05). As for RT-qPCR, the ΔCq of Pim-1 in the ADPC (6.15±0.34) and AIPC (4.56±0.23) groups were significantly different compared with the ADT group (5.11±0.21; P<0.05). Using 2^−ΔΔCq as a relative quantification method to analyze the data, the amplification products of Pim-1 increased by 2.05 and 3.01 times in the ADT and AIPC groups, respectively. ELISA demonstrated the following: The serum concentration of PSA was 0 ng/ml in the control group, 0.48±0.025 ng/ml in the ADPC group and 0.87±0.023 ng/ml in the AIPC group, which were significantly different compared with the ADT group (0.17±0.032 ng/ml; P<0.01). Upon immunohistochemical staining, the protein expression levels of Pim-1 and AR, respectively, were 0.017±0.0021 and 0.032±0.009 in the ADPC group, 0.024±0.0019 and 0.040±0.011 in the AIPC group, and 0.018±0.0013 and 0.019±0.006 in the ADT group. The protein levels of Pim-1 and AR in the ADPC and AIPC groups were significantly different compared with the ADT group (P<0.01). In addition, an orthotopic prostate cancer animal model of ADT was successfully established in the current study, and further investigation revealed that ADT did not affect the expression of Pim-1 at the gene or protein levels; thus, it is hypothesized that Pim-1 may be important in the proliferation and differentiation of prostate cancer during ADT.