A Study Of The Effect Of GOLPH3L On The Biological Behavior And The Sensitivity To Chemotherapy Of Prostate Cancer Cells And Its Mechanism

Research purpose:Prostate cancer is a serious threat to men's health.Endocrine therapy and chemotherapy is metastatic castration resistant first-line treatment for prostate cancer,but the long-term curative effect is not ideal,to improve the effect of the treatment of prostate cancer,solve the problem of drug resistance,need to explore new research targets,hope by blocking the targets can effectively inhibit the occurrence and development of prostate cancer,inhibit or reverse prostate cancer drug resistance.GOLPH3 L proved to be a new oncogene in rhabdomyosarcoma,ovarian cancer and cervical cancer.The purpose of this study was to investigate the expression of GOLPH3 L in prostate cancer,and the effect of GOLPH3 L on the biological behavior and the sensitivity to chemotherapy of prostate cancer PC3 cells and its mechanism.Methods: The expression of GOLPH3 L in prostate cancer was determined by WB and IHC,and the expression of GOLPH3 L in PC3 cells was down-regulated by si RNA.The effects of silencing GOLPH3 L on PC3 cell proliferation,clonal formation,tumor formation in vitro and sensitivity to docetaxel were determined by MTS and plate cloning and soft agar colony formation experiments.Transwell assay was used to determine the effect of silencing GOLPH3 L on the migration and invasion of PC3 cells.The effects of silencing GOLPH3 L on the apoptosis and cycle of PC3 cells were analyzed by flow cytometry.WB was used to analyze the expression of GOLPH3 in prostate cells and the downstream signaling of GOLPH3 L in PC3 cells.The effects of silencing GOLPH3 on PC3 cell clonal formation and tumor formation in vitro were determined by plate clonal formation experiment and soft agar colony formation experiment.Results:The expression of GOLPH3 L was significantly upregulated in prostate cancer tissues and prostate cancer cell lines.In prostate cancer PC3 cells,GOLPH3 L and GOLPH3 showed synergistic expression.Silencing GOLPH3 L significantly inhibited PC3 cell proliferation,clonal formation,tumor formation,migration and invasion in vitro,increased PC3 cell sensitivity to docetaxel chemotherapy,and promoted PC3 cell apoptosis.Silencing GOLPH3 L regulates cell cycle by decelerating S-G2 phase transition in PC3 cells.Silencing GOLPH3 L significantly down-regulated GOLPH3,NF-?B(P65)protein expression in PC3 cells.Silencing GOLPH3 also significantly inhibited the clonal formation and tumor formation of PC3 cells in vitro.Silencing GOLPH3 L may inhibit the proliferation of prostate cancer cells and increase susceptibility to docetaxel by down-regulating the GOLPH3/NF-?B(P65)signaling axis.Conclusions:GOLPH3L is a potential therapeutic target for prostate cancer.