关键词: 神经胶质瘤, 肿瘤干细胞, 细胞增殖, 微RNAs, 莱菔硫烷, miR-124

Abstract: Abstract: Objective To investigate the effect of sulfuraphane (SFN) on proliferation of glioma stem cell line SWO 38, and its mechanism threreof. Methods Cell proliferation of SWO-38 treated with SFN was measured by cell proliferation assay. Clone formation experiment, tumor sphere formation experiment and Western blotting method were applied to detect the ability of cell clone formation and tumor sphere formation, and the expression of stemness relative genes, such as β-catenin, Oct4, Sox-2 and c-Myc. The effects of SFN and/or miR-124 inhibitor (miR-124i) on the expression of stemness relative genes were compared. Changes of miRNAs (miRNA-9, 21, 221, 124, 128 and 181) induced by SFN were measured by real time quantity PCR. Results SFN suppressed the proliferation of SWO-38 cells in a dose-dependent manner, in which IC50 was (26.41±2.13) μmol/L. SFN also decreased the ability of forming cell clone and tumor sphere, as well as the expression of stemness relative genes (β-catenin, Oct4, Sox-2 and c-Myc) in a dose-dependent manner. At the same time, SFN led to the change in many miRNAs, during which SFN increased the transcription of miR- 124 (-5.9-fold) and miR-128 (-2.6-fold), and decreased the transcription of miR-9, miR-21 and miR-221. Compared to the blank control, the expression levels of β-catenin, Oct4, and Sox-2 were significantly increased in miR-124i group. On the other hand, the expressions of above genes were also higher in combined group, which was treated with miR-124i and SFN than those in SFN group, but lower than those of miR-124i group. Conclusion SFN can efficiently inhibit the proliferation of giloma stem cells in SWO 38 cell line through miR-124/(β-catenin/Sox-2/Oct4) signaling pathway

Key words: glioma, neoplastic stem cells, cell proliferation, microRNAs, sulforaphane, miR-124