STI571对恶性多发性神经胶质母细胞瘤(GBM)的体外抑瘤作用  

Biological Activity of a Novel Tyrosine Kinase Inhibitor of the 2-Phenylaminopyrimidine Class, STI571 on Human Glioblastoma Cells

作　　者：任欢[1] 李殿俊[1] Rainov NG 

机构地区：[1]哈尔滨医科大学免疫学教研室,哈尔滨市150086 [2]英国利物浦大学神经医学系

出　　处：《中国肿瘤临床》2004年第15期856-859,共4页Chinese Journal of Clinical Oncology

基　　金：黑龙江省自然科学基金资助(编号:DO122)

摘　　要：目的:研究酪氨酸激酶抑制剂(STI571)对恶性胶质瘤细胞的肿瘤生物学调节作用。方法:用免疫组化法探查血小板源生长因子(PDGF)及其受体在T98G,U87MG,LNZ308,RG四种胶质瘤细胞的表达;MTT法用于检查STI571/TMZ单独或联合应用对胶质瘤细胞的增殖抑制作用,STI571诱导的细胞凋亡途径由流式细胞仪检测,免疫印迹杂交法用来探查STI571抵抗细胞的蛋白激酶网络变化。结果:所用胶质瘤细胞均不同程度的表达PDGF及受体。STI571与TMZ相互协同作用于胶质瘤细胞株T98G;10滋mol/LSTI571可部分抑制所测胶质瘤细胞增殖、可完全抑制其形成集落;高于10滋mol/L浓度的STI571可快速诱导胶质瘤细胞凋亡或坏死;胶质瘤细胞株T98G与STI571长期共培养后,瘤细胞蛋白激酶网络有较大改变。结论:研究表明,PDGF受体酪氨酸激酶抑制剂STI571有较强的抑制恶性胶质瘤细胞(GBM)增殖的作用并可能与其他化疗药物协同抗肿瘤。Objectives: To investigate receptor tyrosine kinase STI571, its regulation of tumor bio-functions on human glioblastoma cells. Methods: The expression of PDGF and receptors were detected by immunocytochemistry; MTT assays /Soft agar colony formation assays were performed to determine the tumor cell growth/colony formation inhibition under STI571, Temozolomide(TMZ), alone and in combination; Synergy was evaluated by Chou-Talalay method; Flow cytometric assays were carried out to discover the tumor cell death induced by STI571. Immuno-blot based kinase screening was performed on some cells. Results: 10 (M or above STI571 can completely or partial inhibit glioma cell growth and colony formation, respectively. STI571 and TMZ are synergic on inhibiting T98G growth, not the others; Higher concentration STI571 induced mixed apoptosis or necrosis; In addition, protein kinase screen indicated STI571 resistant T98G more active of cell cycle progression. Conclusion: STI571 shows considerable activity against malignant glioma cells and may act synergistically with chemotherapy drugs.

关 键 词：ST1571 酪氨酸激酶抑制剂 恶性胶质母细胞瘤(GBM) 

分 类 号：R73-3[医药卫生—肿瘤]