SERUM AND GLUCOCORTICOID-INDUCED KINASE 1 INHIBITS APOPTOSIS IN PROSTATE CANCER BY PHOSPHORYLATING FOXO3A

Sheng Li, Libin Zhou^*, Tielin Wu, Min Yin, Huimin Long

Department of Urology Surgery, Li Huili Hospital of Ningbo Medical Center, Ningbo, City, Zhejiang Province, 315000, China

Objective: To observe and analyse the role of serum and glucocorticoid-induced kinase 1 (SGK1) in inhibiting the apoptosis of prostate cancer cells by regulating the phosphorylation of Foxo3a. 

Methods: PC3 cells were transfected with SGK1 interfering slow virus plasmids, SGK1 overexpressing plasmids and corresponding empty plasmids, labelled as SGK1 interfering group, SGK1 overexpressing group and control group, respectively. The apoptosis rate was detected by flow cytometry and the expression levels of SGK1, Foxo3a and corresponding phosphorylated proteins were detected by western blotting. The SGK1 overexpression group was further transfected with Foxo3a small interference plasmid and control plasmid, labelled as SGK1 overexpression-Foxo3a interference group and SGK1 overexpression-control group, and SGK1 overexpression-blank group, respectively, to detect the apoptosis rate, SGK1, Foxo3a and corresponding phosphorylated protein expression levels in each group. 

Results: Phosphorylation of Foxo3a (Thr-32) decreased compared with control group and the blank group, phosphorylation SGK1 interference group, SGK1 (Ser-78) and phosphorylated Foxo3a (Ser-253). the apoptosis rate, SGK1 in express group phosphorylation SGK1 (Ser-78) and phosphorylated Foxo3a (Ser-253), and phosphorylation Foxo3a (Thr-32) increased, the decrease in the total cell apoptosis rate, the difference had statistical significance (P<0.05). Foxo3a in the SGK1 interference group was concentrated in the nucleus, while a large amount of Foxo3a was transferred from the nucleus to the cytoplasm in the SGK1 overexpression group, the control group and the blank group. The levels of Foxo3a, phosphorylated Foxo3a (Ser-253) and phosphorylated Foxo3a (Thr-32) decreased and the total apoptosis rate increased in the SGK1 overexpression control group and SGK1 overexpression blank group, respectively (P<0.05).

Conclusion: SGK1-induced Foxo3a phosphorylation may be one of the mechanisms responsible for the abnormally decreased apoptosis rate of prostate cancer cells.