Sirtuin-7 knockdown inhibits the growth of endometrial cancer cells by inducing apoptosis via the NF-κB signaling pathway.

Abstract

Sirtuin-7 is an evolutionarily conserved NAD-dependent deacetylase, which serves an important role in carcinogenesis. However, the potential mechanism of sirtuin-7 in endometrial cancer has not yet been investigated. The purpose of the present study was to investigate whether sirtuin-7 exhibits inhibitory effects on endometrial cancer cells. The potential mechanisms mediated by sirtuin-7 in endometrial cancer cells were also investigated. The expression levels of sirtuin-7 in endometrial cancer cells were compared with normal endometrial cells using western blotting. The results demonstrated that sirtuin-7 is overexpressed in endometrial cancer cells compared with normal endometrial cells. The downregulation of sirtuin-7 inhibited the growth and invasiveness of endometrial cancer cells. The knockdown of sirtuin-7 was observed to increase the sensitivity of the endometrial cancer cells to cisplatin treatment in vitro. An investigation into the potential molecular mechanism demonstrated that sirtuin-7 knockdown promoted the apoptosis of endometrial cancer cells by regulating the nuclear factor (NF)-κB signaling pathway. The knockdown of sirtuin-7 inhibited NF-κB expression and resulted in a decrease in the expression of NF-κB target proteins that are anti-apoptotic: Bcl-xl, Bcl-2 and Mcl-1. Sirtuin-7 knockdown also resulted in an increase of the NF-κB target proteins that are pro-apoptotic: Caspase-3, Bad and Bax. In conclusion, the present study demonstrated that sirtuin-7 knockdown was able to markedly inhibit the growth of endometrial cancer cells, suggesting that sirtuin-7 may be a potential therapeutic target for endometrial cancer therapy.