Beauchesne P, Bertrand S, N'guyen M J, Christianson T, Dore J F, Mornex F, Bonner J A
Department of Radiation Oncology, Mayo Clinic Center, Rochester, Minnesota, USA.
Cancer Chemother Pharmacol. 1998;41(2):93-7. doi: 10.1007/s002800050713.
Malignant gliomas display aggressive local behavior and are not cured by existing therapy. Etoposide, a topoisomerase-II-inhibitor agent, is one of the most active and useful antineoplastic agents. However, etoposide is not usually used on these tumors. We undertook an in vitro study to prove that etoposide is a useful drug for malignant gliomas.
Five human glioma cell lines were the basis for this study. Following exposure to various concentrations of etoposide, the glioma cell lines were found to be sensitive; the median concentration inhibiting the number of cells by 50% (IC50) was 8.76 microg/ml (range 8-15.8 microg/ml). Since topoisomerase II is the critical target for etoposide, it was of interest to determine the topoisomerase II activity (decatenation of kinetoplast DNA isolated from Cryphtidia fasciculata) and the etoposide-induced inhibition of topoisomerase II activity.
The topoisomerase II activity was homogeneous in glioma cell lines (average of 50% decatenation with 7,000 cells), and topoisomerase II was the target of the etoposide.
Our results suggest that topoiomerase II-reactive agents may prove to be clinically useful drugs for patients with malignant gliomas.
恶性胶质瘤表现出侵袭性的局部行为，现有治疗方法无法将其治愈。依托泊苷是一种拓扑异构酶-II抑制剂，是最具活性且有效的抗肿瘤药物之一。然而，依托泊苷通常并不用于这些肿瘤的治疗。我们进行了一项体外研究，以证明依托泊苷对恶性胶质瘤是一种有效的药物。
本研究以5种人类胶质瘤细胞系为基础。在暴露于不同浓度的依托泊苷后，发现这些胶质瘤细胞系具有敏感性；抑制细胞数量50%的中位浓度（IC50）为8.76微克/毫升（范围为8 - 15.8微克/毫升）。由于拓扑异构酶II是依托泊苷的关键靶点，因此测定拓扑异构酶II活性（从束状隐鞭虫分离的动质体DNA的解连环作用）以及依托泊苷对拓扑异构酶II活性的诱导抑制作用就很有意义。
胶质瘤细胞系中的拓扑异构酶II活性是一致的（7000个细胞平均解连环作用为50%），且拓扑异构酶II是依托泊苷的作用靶点。
我们的结果表明，拓扑异构酶II反应性药物可能被证明是对恶性胶质瘤患者具有临床疗效的药物。
