Function And Mechanism Of Ubenimex In Prostate Cancer Cells In Vitro

Background:Former reseach has demonstrated that Aminopeptidase N (APN) expression is closely correlated with metastasis,such as gastrointestinal tumors. Ubenimex, an APN inhibitor, is widely used as adjunct therapy for cancer. However, due to its low expression, it is rarely used to treat prostate cancer. Recently, the induction of autophagy as a molecular mechanism has been strongly connected with tumor cell death,and the induction of autophagic cell death is related to lots of cell signal pathways,such as JNK,Akt,NF-kB,and so an.Materials and Methods:LNCaP,and PC-3 cell lines were used in the study.We added the different dose of ubenimex,which shows 0,0.25mg/ml,0.5mg/ml, 1mg/ml.then cell viability was measured using a curve growth analysis and WST-8 proliferation assay. Autophagic cell death was assessed using LDH,fluorescent microscope and acridine orange/ethidium bromide (AO/EB) staining. Protein expression were assayed using western blotting analyses.Autophagosomes were evaluated using transmission electron microscopy. Wound-healing migration assays were performed to determine the migration of PC-3 cells. Moreover, matrigel invasion assays demonstrated that the migration and invasion of PC-3 cells were markedly suppressed by ubenimex.Results:APN expression differed between metastatic and non-metastatic prostate cancer cells,which expression is higher in PC-3,the metastatic prostate cancer cells (P<0.05). In addition, ubenimex could inhibit APN expression in prostate cancer cells(P<0.05). Furthermore, ubenimex could inhibit PC-3 cell proliferation, along with the migration and invasion of prostate cancer cell lines(P<0.05). Finally, ubenimex induces autophagic cell death of prostate cancer cells through JNK pathway(P<0.05).Conclusion:Ubenimex can inhibit cell migration and invasion in prostate cancer cells by downregulating APN expression. Moreover, this drug can also inhibit the proliferation of PC-3. Furthermore, ubenimex can induce autophagic cell death through JNK pathway in both metastatic and non-metastatic prostate cancer cells.