Effect of sodium butyrate combined with TRAIL on biological behaviors of lung cancer stem cells / 中国组织工程研究

ABSTRACT

BACKGROUND:Sodium butyrate, a histone deacetylase inhibitor, can inhibit cell proliferation, and induce apoptosis and differentiation of various cancer cells. However, the role of sodium butyrate combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on lung cancer stem cells remains unclear. OBJECTIVE:To explore the effect of sodium butyrate combined with TRAIL on biological behaviors of lung cancer stem cells. METHODS:Magnetic bead separation was used to separate lung cancer stem cells (CD133+) from human lung adenocarcinoma A549 cells. After the lung cancer stem cells were treated with simple DMEM/F12, DMEM/F12 containing sodium butyrate (5 mmol/L), TRAIL (50 μg/L) or sodium butyrate combined with TRAIL, the cell proliferation within 96 hours of culture was determined by MTT assay; the apoptosis within 24 hours of culture was measured by flow cytometry; the cell migration within 48 hours of culture was detected by cell scratch test; the expression levels of pluripotent transcription factors (Oct4, Sox2 and Nanog) within 48 hours of culture were detected using western blot analysis. RESULTS AND CONCLUSION:The CD133+ lung cancer stem cells were successfully enriched from human lung adenocarcinoma A549 cells. MTT assay showed that sodium butyrate and TRAIL significantly inhibited the proliferation of lung cancer stem cells (P< 0.05), and the combination effect was even stronger (P < 0.05). Results from flow cytometry analysis and scratch test showed that sodium butyrate or TRAIL induced apoptosis and inhibited cell migration of lung cancer stem cells (P < 0.05), and the combination of sodium butyrate and TRAIL showed a stronger effect (P < 0.05). In addition, the expression levels of Oct4, Sox2 and Nanog were significantly down-regulated by sodium butyrate (P < 0.05), TRAIL or sodium butyrate combined with TRAIL, and the combination effect was stronger (P < 0.05). In conclusion, sodium butyrate and TRAIL have synergistic effects on lung cancer stem cells, indicating a new way for treatment of lung cancer.