Down-regulation of Bcl-2 and Bcl-xL expression with bispecific antisense treatment in glioblastoma cell lines induce cell death
Down-regulation of Bcl-2 and Bcl-xL expression with bispecific antisense treatment in glioblastoma cell lines induce cell death
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DOI：
10.1046/j.1471-4159.2003.01522.x
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发表时间：
2003-01-01
影响因子：
4.7
通讯作者：
Rich, KM
中科院分区：
文献类型：
--
作者：
Jiang, ZH;Zheng, X;Rich, KM
检测抗凋亡蛋白Bcl-2和Bcl-xL在胶质母细胞瘤中的功能。细胞，发现Bcl-2和Bcl-xL的表达在来自7个早期传代细胞系的蛋白质裂解物中升高，所述细胞系来源于人成胶质细胞瘤肿瘤，与非肿瘤性胶质细胞相比。bcl-2/bcl-xL双特异性反义寡核苷酸下调胶质母细胞瘤细胞系U87和NS 008中bcl-2和bcl-xL的表达导致细胞自发死亡。细胞死亡的机制是部分依赖半胱天冬酶。bcl-2/bcl-xL反义核酸诱导的细胞凋亡与caspase 6和caspase 7有关，而与caspase 3无关。有趣的是，蛋白质印迹法未能证明在两个七个胶质母细胞瘤细胞系检查的caspase 3的表达。这些数据支持Bcl-2和Bcl-xL在防止胶质母细胞瘤细胞中的细胞死亡中是重要的假设。它还表明，有功能途径能够成功完成半胱天冬酶依赖性细胞死亡的胶质瘤。这些发现支持bcl-2/bcl-xL双特异性反义寡核苷酸疗法作为增强胶质母细胞瘤患者中半胱天冬酶依赖性细胞死亡的治疗策略的潜在作用。
The functions of the antiapoptotic proteins Bcl-2 and Bcl-xL were examined in glioblastoma. cells, Expression of both Bcl-2 and Bcl-xL were found to be elevated in protein lysates from seven early passage cell lines derived from human glioblastoma tumors compared with non-neoplastic glial cells. Downregulation of both bcl-2 and bcl-xL expression in glioblastoma cell lines U87 and NS008 with bcl-2/bcl-xL bispecific antisense oligonucleotide resulted in spontaneous cell death. The mechanism of cell death was partially caspase-dependent. Executioner caspase 6 and caspase 7, but not caspase 3, were involved in apoptosis induced by bcl-2/bcl-xL antisense treatment. Interestingly, western blots failed to demonstrate expression of caspase 3 in two of the seven glioblastoma cell lines examined. The data support the hypothesis that Bcl-2 and Bcl-xL are important in preventing cell death in glioblastoma cells. It also suggests that there are functional pathways capable of successful completion of caspase-dependent cell death in gliomas. These findings support a potential role of bcl-2/bcl-xL bispecifc antisense oligonucleotide therapy as a treatment strategy to enhance caspase-dependent cell death in patients with glioblastoma.