Fluvastatin-mediated down-regulation of SATB1 affects aggressive phenotypes of human non-small-cell lung cancer cell line H292

Abstract

AimsFluvastatin reduces tumor proliferation and increased apoptotic activity in various cancers. Special AT-rich sequence binding protein 1 (SATB1) is a genome organizer that reprogrammes the gene transcription profiles of tumors to promote growth and metastasis. The antitumor effect and molecular mechanisms of fluvastatin on lung cancer is poorly understood. This study aimed to investigate the antitumor effect of fluvastatin on lung cancer and its possible mechanics. Main methodsCell viability assay was used to examine the inhibition of fluvastatin on proliferation of H292 cells. In order to investigate the antitumor mechanics, SATB1 knock-down H292 cells was constructed by lentiviral transfection. RT-PCR and Western blot were performed to examine the effects of fluvastatin on expression of SATB1 and Wnt/β-catenin signaling components. Key findingsFluvastatin significantly inhibited proliferation and invasion of H292 cells in a time- and dose-dependent manner and promoted the apoptosis (p < 0.05). The expression of SATB1 was down-regulated by fluvastatin in a dose-dependent manner. The proliferation and invasion of SATB1-shRNA cells was significantly suppressed, and the apoptosis was significantly enhanced (p < 0.05). We also show that the common target genes were regulated by SATB1 and Wnt/β-catenin pathway simultaneously. There may be a functional link between SATB1 and Wnt/β-catenin pathway. SignificanceWe presented a possible mechanism of statins that fluvastatin significantly suppressed the in vitro tumor progression of H292 cells possibly by down-regulation of SATB1 via Wnt/β-catenin pathway, which provided new therapeutic possibilities for more cancers driven by hyperexpression of SATB1 and Wnt/β-catenin pathway.