Regulatory effects of prostate specific membrane antigen on proliferatation, survival and metabolism of prostate cancer cells via p38 pathway

Abstract

Objective To test the role of prostate specific membrane antigen (PSMA) regulating related pathways in the proliferatation,survival and metabolism of prostate cancer cells.Methods LNCaP cells had been stably transfected with lentivirus-mediated shRNA for PSMA silencing in previous study.The efficacy of PSMA knockdown was testified in LNCaP cell line.By using this PSMA-LNCaP cell line,the expression of PSMA and phospho-p38 (p-p38) detected by using Western blotting was compared among groups.Immunofluorescence was used to confirm the change of p-p38 in cells.Cell viability and migration were measured by cell counting kit-8 reagent and Transwell analysis respectively.Flow cytometry was employed to evaluate the cell survival.P38 pathway inhibitor (SB203582) was used in the culture medium to determine the role of p38 in the prostate cancer cells regulated by PSMA.Results After silencing the expression of PSMA,the expression level of p-p38 was decreased by approximate 40％ as compared with the blank and non-interference groups (P ＜ 0.05).When the cells were incubated with SB203582,the p-p38 expression in three groups was at a low level and no significant difference was found among groups (P ＞0.05).The results of immunofluorescence further proved the relationship between PSMA and p-p38.Decrease of cell viability,migration and survival was observed upon PSMA silencing.SB203580,a specific inhibitor of p38 mitogen-activated protein kinase (MAPK) pathway,also reduced the proliferation,migration and survival of LNCaP cells.Conclusion These data suggest PSMA may stimulate proliferation,migration and survival of prostate cancer cells through p38 MAPK pathway,revealing a novel mechanism for PSMA playing positive roles in LNCaP cells. Key words: Prostate specific membrane antigen; p38; Prostate cancer; Cell signaling pathway