Winter S, Roth W, Dichgans J, Weller M
Department of Neurology, University of Tübingen, School of Medicine, Germany.
Eur J Pharmacol. 1998 Jan 12;341(2-3):323-8. doi: 10.1016/s0014-2999(97)01478-7.
Teniposide (VM26) enhanced the anti-glioma activity of the cytotoxic cytokine, CD95 ligand. Synergy was observed at concentrations of teniposide that were insufficient for cleavable DNA topoisomerase II complex formation. CD95 ligand did not modulate the formation or removal of such complexes after teniposide treatment. These processes were also unaffected by ectopic expression of bcl-2. Teniposide enhanced CD95 expression in a glioma cell line with wild-type p53 (LN-229) but not in two p53 mutant cell lines (T98G, LN-308). Forced expression of a transdominant negative p53 mutant prevented the teniposide induced augmentation of CD95 expression in LN-229 cells but did not prevent the synergy of CD95 ligand and teniposide. Teniposide did not alter CD95 ligand expression, and forced expression of CD95 did not modulate sensitivity to VM26. Thus, teniposide-induced DNA lesions and alterations in CD95 or CD95 ligand are not necessary for teniposide-induced sensitization of human malignant glioma cells to CD95-mediated apoptosis.
替尼泊苷（VM26）增强了细胞毒性细胞因子CD95配体的抗胶质瘤活性。在不足以形成可裂解DNA拓扑异构酶II复合物的替尼泊苷浓度下观察到了协同作用。在替尼泊苷处理后，CD95配体并未调节此类复合物的形成或去除。这些过程也不受bcl-2异位表达的影响。替尼泊苷在具有野生型p53的胶质瘤细胞系（LN-229）中增强了CD95表达，但在两个p53突变细胞系（T98G、LN-308）中未增强。转显性负性p53突变体的强制表达阻止了替尼泊苷诱导的LN-229细胞中CD95表达的增加，但并未阻止CD95配体与替尼泊苷的协同作用。替尼泊苷未改变CD95配体的表达，CD95的强制表达也未调节对VM26的敏感性。因此，替尼泊苷诱导的DNA损伤以及CD95或CD95配体的改变对于替尼泊苷诱导的人恶性胶质瘤细胞对CD95介导的凋亡的致敏作用并非必要。
