Abstract
The etiological or clinicopathological significance of serum glucocorticoid-induced protein kinase 1 (SGK1) in lung adenocarcinoma remains unclear. This study aimed to investigate the role of SGK1 in the development and progression of human lung adenocarcinoma and the effects of targeted inhibition of intrinsic SGK1 expression on the proliferation of lung adenocarcinoma cells. SGK1 protein expression in 150 human cases of lung adenocarcinoma was detected by immunohistochemical analysis, and the relationships between SGK1 expression and clinicopathological features were assessed. In addition, endogenous SGK1 profiles were determined in seven lung adenocarcinoma cell lines. Cell proliferation, cell cycle distribution, and apoptosis were characterized in the absence and presence of SGK1 inhibitors. Compared to the adjacent normal tissues, significantly higher SGK1 expression levels were detected in the cytoplasm in cancerous lung adenocarcinoma tissues. Besides, SGK1 expression correlated with lymph node metastasis, distant metastasis, and pathological staging. Univariate analysis suggested that overexpression of this protein correlated significantly with a poor prognosis. Cultured lung adenocarcinoma cells expressed relatively high SGK1 levels, and inhibition of this protein was associated with G2 cell cycle arrest and reduced cyclin B1 and cdc2 expression. Pharmacological SGK1 inhibition experiments corroborated the role of this protein in cell cycle progression. SGK1 expression correlated closely with lung adenocarcinoma progression and could be used as a prognostic marker. Endogenous SGK1 inhibition abrogated lung adenocarcinoma cell proliferation via G2/M-phase cell cycle arrest, which was likely mediated by the concerted actions of cell cycle regulators.