Inhibitory Effect Of C646Combined With Anacardic Acid On Androgen-independent Prostate Cancer Cells In Vitro

Purpose: To evaluate the effects of C646combined with anacardic acid(AA) on theproliferation, apoptosis, migration, and cell cycles of the androgen-independent prostatecancer(AIPC) cell line, investigate the mechanisms and provide a theoretical basis for vivoexperiments and clinical studies.Materials and Methods: We observed the toxicity on three kinds of prostate cancercell lines and one kind of normol prostate epithelial cells after been treated with C646orAA by MTS, and then got the more toxic AIPC to continue. Four groups were designed innext experiment: control, C646, AA, and combination(C646+AA). The inhibitory effect ofproliferation, migration, and the ability to induce apoptosis, changes of cell cycles weredetected by MTS, Trans-well, flow cytometry, inverted microscope and so on. Combinedwith the existing research, we have analyzed the possible mechanism of the action.Results: MTS revealed that the toxic effects of two drugs are similar, expressed asLNCaP>DU-145>PC-3>PNT1A. We choose the more cytotoxicity one ofandrogen-independent prostate cancer cell line DU-145for further experiments. The halfinhibitory concentration of C646is about20μmol/L, and the half inhibitory concentrationof AA is about75μmol/L, but this concentration of AA have greater impact on normalprostate cells, and we found little effect on normal cells when the concentration are lessthan25μmol/L, this was the concentration we used in the next experiment. After treatedDU-145with drugs in C646, AA and combination group,(1) MTS showed that cell viability rates were0.529,0.763,0.239in each group, and it was more cytotoxicity in thecombination group(P<0.05);(2) The flow cytometry test and Western Blot test showed thatthe cell apoptosis rate was significant increased in combination group(P<0.05);(3)Trans-well test showed that the proportion of migrating cells accounted from the controlgroup were77.82%,88.35%and65.19%in each group, it was more significant in thecombination group(P<0.05);(4) PI stain and flow cytometry assay showed that there wereno significant effect on the cell cycle(P>0.05).Conclusions: C646and AA could inhibit the DU-145through blocking cellularproliferation and inducing apoptosis in vitro alone, and significantly in combination; Theyhave a certain degree of inhibition on cell migration, and significantly in combination too;The two drugs had no significant effect on the cell cycle.