Vita J R, Edwalds G M, Gorey T, Housepian E M, Fetell M R, Guarini L, Langer J A, Fisher P B
Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
Anticancer Res. 1988 May-Jun;8(3):297-302.
In the present study we have evaluated the effect of recombinant human fibroblast, IFN-beta ser, and immune, IFN-gamma, interferon, alone and in combination, on the proliferation of fifteen early passage human glioblastoma cell cultures. Explant cultures were established from glioblastoma tumor tissue obtained at the time of surgery. After sufficient outgrowth, cultures were dispersed with trypsin/versene and maintained as independent cell lines. IFN-beta ser induced a greater than or equal to 50% reduction in the 7 day growth of 6 of the 15 cultures. The majority of cultures, 9 of 15, displayed less than or equal to 50% growth suppression in comparison with control cultures after 7 days exposure to 2000 Units/ml of IFN-beta ser. When treated with 2000 Units/ml of IFN-gamma, only 1 of the 15 glioblastoma cultures exhibited a greater than or equal to 50% reduction in growth. In contrast, when treated with the combination of IFN-beta ser plus IFN-gamma, 1000 Units/ml of each interferon preparation, 12 of 15 cultures were inhibited by greater than or equal to 50% after 7 days growth. The combination of interferons was effective in suppressing glioblastoma growth both in cultures displaying relative sensitivity and those exhibiting innate resistance to either or both types of interferon when employed alone. One glioblastoma culture, G-7, was studied through 45 passages and displayed the same sensitivity at different passages to growth inhibition when exposed to IFN-beta ser, IFN-gamma or both interferons. Based on previous clinical studies indicating that IFN-beta or IFN-gamma when administered alone to patients do not generally alter the clinical progression of malignant gliomas, the present results suggest that the combination of IFN-beta plus IFN-gamma may prove more effective than either agent alone in the clinical treatment of patients with glioblastoma multiforme.
在本研究中，我们评估了重组人成纤维细胞干扰素β（IFN-βser）和免疫干扰素γ单独及联合使用对15种早期传代人胶质母细胞瘤细胞培养物增殖的影响。外植体培养物由手术时获取的胶质母细胞瘤肿瘤组织建立。在充分生长后，用胰蛋白酶/平衡盐溶液分散培养物，并作为独立细胞系维持培养。IFN-βser使15种培养物中的6种在7天生长中减少了大于或等于50%。在暴露于2000单位/毫升的IFN-βser 7天后，大多数培养物（15种中的9种）与对照培养物相比，生长抑制小于或等于50%。当用2000单位/毫升的IFN-γ处理时，15种胶质母细胞瘤培养物中只有1种生长减少大于或等于50%。相比之下，当用IFN-βser加IFN-γ联合处理时，每种干扰素制剂1000单位/毫升，15种培养物中的12种在7天生长后被抑制大于或等于50%。干扰素联合使用在单独使用时对其中一种或两种干扰素显示出相对敏感性或固有抗性的培养物中，均能有效抑制胶质母细胞瘤生长。一种胶质母细胞瘤培养物G-7经过45代研究，在不同代次暴露于IFN-βser、IFN-γ或两种干扰素时，对生长抑制表现出相同的敏感性。基于先前的临床研究表明，单独给患者使用IFN-β或IFN-γ通常不会改变恶性胶质瘤的临床进展，目前的结果表明，IFN-β加IFN-γ联合使用在多形性胶质母细胞瘤患者的临床治疗中可能比单独使用任何一种药物更有效。
