Hong-Yu Xu1, Jian-Xin Xue2, Hui Gao3, Fei-Fei Na2, Hua Li3, Tao Zhang4, You Lu5. 1. Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, China; Department of Oncology, The General Hospital of Western Theater Command, Chengdu, China. 2. Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, China. 3. Department of Oncology, The General Hospital of Western Theater Command, Chengdu, China. 4. Department of Oncology, The General Hospital of Western Theater Command, Chengdu, China. Electronic address: zhangtao269@126.com. 5. Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, China. Electronic address: radyoulu@hotmail.com.
Abstract
AIMS: Fluvastatin 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 METHODS: Cell 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 FINDINGS: Fluvastatin 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. SIGNIFICANCE: We 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.
AIMS: Fluvastatin 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 METHODS: Cell 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 FINDINGS:Fluvastatin 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. SIGNIFICANCE: We 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.