Weller M, Rieger J, Grimmel C, Van Meir E G, De Tribolet N, Krajewski S, Reed J C, von Deimling A, Dichgans J
Department of Neurology, University of Tübingen, Germany.
Int J Cancer. 1998 Dec 18;79(6):640-4. doi: 10.1002/(sici)1097-0215(19981218)79:6<640::aid-ijc15>3.0.co;2-z.
Less than 30% of malignant gliomas respond to adjuvant chemotherapy. Here, we asked whether alterations in the p53 and RB pathways and the expression of six BCL-2 family proteins predicted acute cytotoxicity and clonogenic cell death induced by BCNU, vincristine, cytarabine, teniposide, doxorubicin, camptothecin or beta-lapachone in 12 human malignant glioma cell lines. Neither wild-type p53 status, nor p53 protein accumulation, nor p21 or MDM-2 levels, nor differential expression of BCL-2 family proteins predicted drug sensitivity, except for an association of BAX with higher beta-lapachone sensitivity in acute cytotoxicity assays. p16 protein expression was associated with high doubling time and chemoresistance. We conclude that some important molecular changes, which are involved in the development of gliomas and attributed a role in regulating vulnerability to apoptosis, may not determine the response to chemotherapy in these tumors.
不到30%的恶性胶质瘤对辅助化疗有反应。在此，我们探讨p53和RB信号通路的改变以及六种BCL-2家族蛋白的表达是否能预测12种人恶性胶质瘤细胞系中由卡莫司汀、长春新碱、阿糖胞苷、替尼泊苷、多柔比星、喜树碱或β-拉帕醌诱导的急性细胞毒性和克隆源性细胞死亡。除了在急性细胞毒性试验中BAX与较高的β-拉帕醌敏感性相关外，野生型p53状态、p53蛋白积累、p21或MDM-2水平以及BCL-2家族蛋白的差异表达均不能预测药物敏感性。p16蛋白表达与高倍增时间和化疗耐药相关。我们得出结论，一些参与胶质瘤发生发展并在调节细胞凋亡易感性中起作用的重要分子变化，可能无法决定这些肿瘤对化疗的反应。
