OBJECTIVE To investigate the effects of aucubin(AU)on the proliferation and tumor growth of prostate cancer(PC)cells by regulating the protein kinase B(Akt)/murine double minute2(MDM2)/p53 signaling pathway.METHODS Prostate cancer cell PC3 were separated into control group,50 μmol/L AU group,100 μmol/L AU group,SC79(Akt activator)group(5 μmol/L),and 100 μmol/L AU+SC79 group.The cell cloning and proliferation ability were investigated;the rate of cell apoptosis and the expressions of Akt/MDM2/p53 signaling pathway-related protein were detected.Meanwhile,xenograft tumor models of nude mice were constructed and separated into tumor group,AU group(80 mg/kg),SC79 group(50 mg/kg),and AU+SC79 group(80 mg/kg AU+50 mg/kg SC79),with 10 mice in each group.They were given relevant medicine,once a day,for 21 d.After the last medication,tumor weight was determined,and the expressions of nucleus-associated antigen(Ki-67)and Akt/MDM2/p53 signaling pathway-related protein were detected in tumor tissue.RESULTS In the cell experiment,compared with control group,the cell clonal formation number,proliferation rate and phosphorylation levels of Akt and MDM2 protein in 50 μmol/L AU and 100 μmol/L AU groups were significantly decreased(P＜0.05),while the cell apoptosis rate and p53 protein expression levels were significantly increased(P＜0.05);however,the change trend of each index in SC79 group was opposite(P＜0.05).Compared with 100 μmol/L AU group,the cell clonal formation number,proliferation rate and phosphorylation levels of Akt and MDM2 protein in 100 μmol/L AU+SC79 group were significantly increased(P＜0.05),while cell apoptosis rate and p53 protein expression levels were significantly decreased(P＜0.05);however,compared with SC79 group,the changing trend of indexes was the opposite(P＜0.05).In the in vivo experiment,compared with the tumor group,the tumor mass and Ki-67 positive expression and the phosphorylation levels of Akt and MDM2 protein in nude mice of AU group were significantly decreased(P＜0.05),and the expression level of p53 protein was significantly increased(P＜0.05),but the changing trend of above indexes of nude mice in SC79 group were opposite(P＜0.05).Compared with AU group,the tumor mass,Ki-67 positive expression and phosphorylation levels of Akt and MDM2 protein in tumor tissues of nude mice in AU+SC79 group were significantly increased(P＜0.05),while the expression level of p53 protein was significantly decreased(P＜0.05);however,compared with SC79 group,the changing trend of above indexes was opposite(P＜0.05).CONCLUSIONS AU can inhibit PC cell proliferation and tumor growth by inhibiting Akt/MDM2/p53 signaling pathway.
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