FOXO3a-ROS Pathway is Involved in Androgen-Induced Proliferation of Prostate Cancer Cell

Background: Although FOXO3a can inhibit the cell proliferation of prostate cancer, its relationship with reactive oxygen species (ROS) in prostate cancer(PCa) has not been reported. Methods: : We analyzed the correlation between the expression of FOXO3a and the antioxidant enzyme catalase in prostate cancer through the UALCAN and GEPIA databases. We also constructed a PPI network of FOXO3a via the STRING database. The mRNA and protein expression of FOXO3a and catalase in LNCaP cells after DHT treatment were detected by qRT-PCR and western blot analysis. The effects of FOXO3a on catalase expression were tested by over-expression and siRNA interference respectively. At the same time, the catalase activity and ROS level in LNCaP cells after DHT treatment were detected. The changes of cell proliferation and ROS in LNCaP by antioxidant were also analyzed. Results: : We found that the catalase expression was down-regulated and has positively correlation with FOXO3a in PCa by public databases. The results of qRT-PCR and western blot showed that the mRNA and protein expression of FOXO3a and catalase were significantly reduced after DHT treatment in the LNCaP cells. Over-expression and knockdown of FOXO3a can also induce the change of catalase expression. DHT treatment can inhibit catalase activity and increase ROS level. We found that antioxidant treatment reduced DHT-induced proliferation and ROS production. Conclusions: : Our data show that the mechanisms by which DHT promotes PCa cell proliferation is that FOXO3a suppresses catalase expression and activates ROS signaling.