Influence Of Curcumin On Proliferation And Apop Tosis Of Prostate Cancer PC-3 Cells By Modulating The PI3K/Akt And NF-κB Signaling Pathways

Objective:Studies have shown that Curcumin can inhibit proliferation and promote apoptosis in a variety of tumor cells in vitro.Our study aims to investigate the effects of Curcumin on the proliferation and apoptosis of prostate cancer PC-3 cells,and explore the possible mechanism.Methods:In this study,we researched the androgen independent prostate cancer PC-3 cells,and set out four groups: control group(add the culture medium without treated with Curcumin),Curcumin group(cells treated with Curcumin),LY294002 group(cells treated with PI3K/Akt inhibitor of LY294002)and combination group(cells treated with both Curcumin and LY294002).The CCK-8 experiment was used for cell proliferation examining and flow cytometry was used to detect the cell apoptosis of each group.The expressions of P53 and Caspase-3 mRNA were assessed by RT-PCR,and the expressions of protein of Akt,P-Akt,NF-kappa B(P65),P-p65,Caspase-3 and P53 were evaluated by Western Blot.Results:Compared with control group,the proliferation of PC-3 cells in each drug intervention groups were inhibited after 24 h,48h and 72h(P<0.05).However,the apoptosis rate of PC-3 cells has been significantly enhanced(P<0.05).These effects in combination group were more significantly than the single-drug groups(P<0.05).The expression of P53 and Caspase-3 in each drug intervention groups were increased compared with control group in both mRNA and protein levels(P<0.05),but the levels of PI3K/Akt and NF-κB(P65)were decreased(P<0.05).And these effects appeared more significantly in combination group than each single-drug groups(P<0.05),while there was no significant different between two single-drug groups in above-mentioned genes and proteins(P>0.05).Conclusion:Curcumin can inhibit the cell proliferation and promote the apoptosis of prostate cancer PC-3 cells,and these effect could be enhanced by LY294002(PI3K inhibitor).Curcumin increased the expression of P53 and Caspase-3 in PC-3 cells on mRNA and protein level.Curcumin reduced the phosphorylation of Akt and NF-kappa B(P65),which then inhibited the activities of Akt kinase and NF-kappa B.These results suggested that the mechanisms of Curcumin on inhibiting the proliferation and promoting the apoptosis of PC-3 cells may be related to the regulations of the PI3K/AKT and NF-kappa B pathways.