SGK1 inhibition induces autophagy-dependent apoptosis via the mTOR-Foxo3a pathway.

ABSTRACT:

Background

Although inhibition of SGK1 has been shown to delay cancer progression, the underlying mechanisms have not yet been elucidated.

Methods

We investigated the cellular responses to GSK650394 treatment and SGK1 silencing (or overexpression) in human prostate cancer (PCa) cell lines and PC3 xenografts by flow cytometry, western blotting, immunofluorescence, transmission electron microscopy and immunohistochemistry.

Results

In the present study, we demonstrated that SGK1 inhibition, mediated by either GSK650394 or SGK1 shRNA, induced G2/M arrest, apoptosis and autophagy. Furthermore, 3MA-mediated autophagy inhibition attenuated SGK1 inhibition-induced apoptosis, suggesting that induction of autophagy precedes apoptosis. Moreover, ectopic expression of SGK1 signif

SUBMITTER: Liu W 

PROVIDER: S-EPMC5674106 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature