Bcl-xL antisense oligonucleotides chemosensitize human glioblastoma cells
Bcl-xL antisense oligonucleotides chemosensitize human glioblastoma cells
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DOI：
10.1159/000063873
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发表时间：
2002-09-01
期刊：
影响因子：
3.3
通讯作者：
Jansen, B
中科院分区：
文献类型：
--
作者：
Guensberg, P;Wacheck, V;Jansen, B
背景：胶质母细胞瘤的化疗耐药与抗细胞凋亡的Bcl2家族成员的表达有关，其中包括Bclxl。方法：用Western blotting检测反义寡核苷酸(ISIS 16009、ISIS 16967)对M059K胶质母细胞瘤细胞bclxl表达的影响。用WST-1比色法和流式细胞仪检测反义寡核苷酸联合紫杉醇诱导细胞凋亡的作用。结果：与使用错配对照寡核苷酸(p<；0.001)相比，反义寡核苷酸介导的bclxl水平的降低导致了对M059K细胞的细胞毒性增强。在Wst-1分析(p<；0.001)和流式细胞仪分析中，降低的诱导细胞凋亡阈值导致对紫杉醇治疗的细胞毒反应显著增强。结论：bc l-xl反义寡核苷酸联合紫杉醇治疗可能是最终改善胶质母细胞瘤临床预后的有效策略。版权所有(C)2002 S.Karger AG，巴塞尔。
Background: Resistance to chemotherapy in glioblastoma has been linked to the expression of antiapoptotic Bcl-2 family members including Bcl-xL. Methods: Bcl-xL expression was specifically reduced in M059K glioblastoma cells with antisense oligonucleotides (ISIS 16009, ISIS 16967) as assessed by Western blotting. Induction of apoptosis by treatment with antisense oligonucleotides in combination with paclitaxel in cell culture was monitored by WST-1 assays and flow cytometric analysis. Results: Antisense oligonucleotide-mediated reduction of Bcl-xL levels led to enhanced cytotoxicity in M059K cells when compared to the use of a mismatch control oligonucleotide (p < 0.001). A decreased threshold for the induction of apoptosis led to significantly enhanced cytotoxic responses to paclitaxel treatment in WST-1 assays (p < 0.001) and flow cytometric analyses. Conclusion: Combination treatment using Bcl-xL antisense oligonucleotides and paclitaxel may qualify as a promising strategy to ultimately improve the clinical outcome of glioblastoma. Copyright (C) 2002 S. Karger AG, Basel.