Effect of inhibitory nuclear factor kappa B on apoptosis of prostate cancer cell line PC-3M inducted by TRAIL

Abstract

Objective To investigate the suppressive effect of pyrrolidine dithiocarbamate on nuclear factor kappa B and to evaluate the effect of enhancement of PDTC on the apoptosis of androgen-independent prostate cancer cell line PC-3M when tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is used. Methods PC-3M cells were divided to different groups according to the treatment with TRAIL (25,50,100 μg/L) or PDTC (25,50,100 μmol/L) or both of them [25/25,25/50,25/100,50/ 25,50/50,50/100 PDTC( μmol/L) ,TRAIL( μg/L) ]. The nuclear translocation of nuclear factor kappa B was evaluated by cell immunohistochemical method and electrophoretic mobility shift assay ( EMSA). The analys of apoptosis was carried out by MTT test and flow cytometry. Results EMSA and cell immunohistochemical analysis showed that the translocation of nuclear factor kappa B can be greatly activated when PC3M cells were treated with TRAIL. The pretreatment of PDTC can block the nuclear translocation and eliminate the protection to cancer cells in apoptosis. In the meantime, as a stong suppressor of nuclear factor kappa B, PDTC is less toxic. The killing effect of TRAIL + PDTC group is obviously more powerful than TRAIL-single group (P <0. 01) . Conclusion The effect of TRAIL will be remarkably neutralized by the activation of nuclear factor kappa B when it deal with androgen-independent prostate cancer cell. On the other hand,TRAIL can significantly and efficiently induce the apoptosis of PC-3M cells when PDTC is pretreated to inhibit the activation of nuclear factor kappa B. Key words: Prostate neoplasm; Carcinoma; Tumor necrosis factor; Nuclear factor kappa B