Yoshida J, Wakabayashi T, Inoue I, Kageyama N
Gan To Kagaku Ryoho. 1985 Jan;12(1):99-104.
Augmentation of cytotoxicity against malignant glioma using a combination of Hu IFN-beta and ACNU was analyzed in vitro from the points of cell growth inhibition and alteration of the DNA histogram. Cytotoxicity was tested by exposing 13 human glioma cell lines to ACNU at a concentration of 5 micrograms/ml and/or Hu IFN-beta at a concentration of 10(3) IU/microliters. These concentrations were considered to be clinical doses. Additive or synergistic effects of the combination of the two agents were observed in all cell lines tested. The cytotoxic effect of two log kill was seen in two cell lines given ACNU treatment alone, one cell line treated with Hu IFN-beta alone, and nine treated with the combination. Flow-cytometry studies of the DNA histogram showed accumulation in the G2+M phase with ACNU and in the S phase with Hu IFN-beta. On the other hand, marked accumulation using the combination in the S phase followed by the G2+M phase was observed and this accumulation lasted for over a week. The present results show an augmentation of antitumor activity and suggest the effectiveness of combined Hu IFN-beta/ACNU therapy in the treatment of patients with malignant glioma.
从细胞生长抑制和DNA直方图改变的角度，在体外分析了使用人干扰素-β（Hu IFN-β）和阿糖胞苷（ACNU）联合用药增强对恶性胶质瘤细胞毒性的情况。通过将13种人胶质瘤细胞系暴露于浓度为5微克/毫升的ACNU和/或浓度为10³国际单位/微升的Hu IFN-β来测试细胞毒性。这些浓度被视为临床剂量。在所有测试的细胞系中均观察到两种药物联合使用的相加或协同作用。单独给予ACNU治疗的两个细胞系、单独用Hu IFN-β治疗的一个细胞系以及联合治疗的九个细胞系中均出现了两个对数杀灭的细胞毒性作用。对DNA直方图的流式细胞术研究显示，ACNU使细胞在G2+M期积累，Hu IFN-β使细胞在S期积累。另一方面，观察到联合用药时细胞在S期显著积累，随后在G2+M期积累，且这种积累持续超过一周。目前的结果表明抗肿瘤活性增强，并提示Hu IFN-β/ACNU联合治疗对恶性胶质瘤患者治疗的有效性。
