siRNA干扰微管微丝交连因子1表达增强替莫唑胺诱导的胶质瘤细胞毒性

发布时间：2018-09-13 12:32

【摘要】：目的研究微管微丝交连因子1(MACF1)在胶质母细胞瘤应对TMZ刺激中的作用。方法替莫唑胺刺激人类胶质母细胞瘤细胞系U87细胞后,通过Western blot、RT-PCR和免疫荧光检测其蛋白表达和细胞内定位。通过RNA干扰技术干扰MACF1的表达。通过裸鼠皮下成瘤和免疫组化检测在活体中TMZ刺激后胶质母细胞瘤中MACF1的表达。结果在体外培养和体内成瘤中均发现替莫唑胺刺激后胶质母细胞瘤MACF1的表达上调(差异约2倍),胞内分布改变(P0.01)。敲除MACF1表达的胶质母细胞瘤细胞在TMZ刺激后其增殖能力下调约45%(P0.01)。替莫唑胺诱导胶质母细胞瘤MACF1表达上调的同时,其细胞骨架发生重组。结论 MACF1可能成为胶质母细胞瘤治疗的一个潜在靶点。
[Abstract]:Objective to study the role of microtubule microfilament linkage factor 1 (MACF1) in the response of glioblastoma to TMZ stimulation. Methods Human glioblastoma cell line U87 was stimulated by temozolidomide and its protein expression and intracellular localization were detected by Western blot,RT-PCR and immunofluorescence. The expression of MACF1 was interfered by RNA interference technique. The expression of MACF1 in glioblastoma stimulated by TMZ in vivo was detected by subcutaneous tumorigenesis and immunohistochemistry in nude mice. Results in vitro culture and in vivo tumorigenesis, the expression of MACF1 in glioblastoma was up-regulated (the difference was about 2 times), and the intracellular distribution was changed (P0.01). The proliferative ability of glioblastoma cells with knockout MACF1 expression was down-regulated by about 45% (P0.01) after TMZ stimulation. MACF1 expression in glioblastoma was up-regulated by temozolamide and the cytoskeleton was recombined. Conclusion MACF1 may be a potential target for the treatment of glioblastoma.
【作者单位】：南方医科大学南方医院神经外科;广州医科大学第六医院神经外科;南方医科大学南方医院临床医学教育中心;中山大学孙逸仙纪念医院神经外科;南方医科大学第五附属医院神经外科;
【基金】：国家自然基金(81372692,81302229,81472315) 广东省自然科学基金(2014A030313167) 高校博士学科点专项科研基金(20134433120014) 国家临床重点专科建设项目经费资助~~
【分类号】：R739.4

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