目的研究骨形成蛋白4（bone morphogenetic protein 4，BMP4）对人胶质瘤干细胞增殖和凋亡的影响。方法在体外以重组人BMP4蛋白干预人胶质瘤U87细胞系来源的胶质瘤干细胞，免疫荧光鉴定胶质瘤干细胞，通过软琼脂克隆实验、流式细胞仪检测，观察BMP4对胶质瘤干细胞增殖和凋亡的影响。结果BMP4能显著抑制胶质瘤干细胞的增殖能力，并诱导其凋亡。BMP4组增殖相关蛋白Cyclin D1表达降低，抗凋亡蛋白Bcl-2表达明显降低，促凋亡蛋白Bax表达显著增多。结论BMP4可显著抑制胶质瘤U87细胞系来源的胶质瘤干细胞的增殖能力，并诱导其凋亡。
MicroRNAs regulate self renewal and differentiation of cancer stem cells.There,we sought to identify the expression of miR-181b in glioma stem cells and investigate the biological effect of miR-181b on glioma stem cells in this study.MiR-181b expression was measured by real-time PCR in glioma stem cells isolated from U87 cells by FACS sorting.After miR-181b was overexpressed in U87 glioma stem cells by miR-181b lentiviral expression vector and/or treatment of temozolomide,secondary neurosphere assay,soft agar colony assay and MTT assay were performed.Compared with U87 cells,the expression of miR-181b was significantly decreased in U87 glioma stem cells.Overexpression of miR-181b decreased neurosphere formation by U87 glioma stem cells in vitro and suppressed colony formation in soft agar,and the cell growth inhibition rates increased in a time-dependent manner in U87 glioma stem cells infected with miR-181b lentivirus.Furthermore,miR-181b had a synergistic effect on temozolomide-induced inhibition of secondary neurosphere and soft agar colony,and on cell growth inhibition rates.MiR-181b functions as a tumor suppressor that suppresses proliferation and reduces chemoresistance to temozolomide in glioma stem cells.
Ping LiXiaoming LuYingyi WangLihua SunChunfa QianWei YanNing LiuYongping YouZhen Fu
