The Study On Molecular Mechanism Of Resistance To TRAIL-induced Apoptosis In Prostate Cancer PC-3Cells

Background and objectives:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) promotesapoptosis in PC-3cells while sparing normal cells. Although many PC-3cells aresensitive to TRAIL-induced apoptosis, some evade theproapoptotic effects of TRAIL.The molecular mechanism of TRAIL-resistant tumors is not fully clear, so it isnecessary to discuss relevant mechanism in this paper.Methods:The PC-3cells were divided into control group (only with medium) and casegroup (processed with different concentrations of TRAIL) for24~72hours in vitro.Cell inhibition rate was determined by MTT method and then TRAIL-resistant PC-3tumors cells were selected. The expression levels of FLIP, DR4, DR5, FADD andcaspase-8genes between TRAIL-sensitive and TRAIL-resistant tumor cells weredetected by Q-PCR.Results:1.TRAIL can inhibit the proliferation of PC-3cell with a certain extent, and thecell average inhibition rate was enhanced duration of action TRAIL; Meanwhile,inhibition rate was also associated with TRAIL concentration, with the strongest cellgrowth inhibition rate at200ng/ml TRAIL.2.The results of Q-PCR detecting expression levels of FLIP, DR4, DR5, FADDand caspase-8gene in TRAIL-resistance PC-3cell was lower than that inTRAIL-sensitive PC-3cell within24h TRAIL effect. As the duration of TRAIL,expression levels of DR4, DR5, FADD and caspase-8gene in TRAIL-resistance PC-3cell was lower than that in TRAIL-sensitive PC-3cell, but expression levels ofFLIP was higher than that in TRAIL-sensitive PC-3cell within72h.Conclusions:1. TRAIL has a certain therapeutic effect for PC-3in vitro, which has a certainrelationship the concentration and therapy time of TRAIL. 2. TRAIL has a certain relationship the concentration of TRAIL, with thestrongest cell growth inhibition rate at200ng/ml TRAIL.3. The express levels of DR4, DR5, FADD, caspase-8and FLIP in PC3celldecreased with a24h treatment of TRAIL; the express levels of DR4, DR5,FADD andcaspase-8decreased and FLIP increased in PC3cell with a72h treatment of TRAIL.