Fleischmann C M, Stanton G J, Fleischmann W R
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555.
Cancer Immunol Immunother. 1994 Sep;39(3):148-54. doi: 10.1007/BF01533379.
Mouse B16 melanoma cells rapidly develop resistance to the antiproliferative effects of interferon alpha (IFN alpha) and interferon beta (IFN beta) when they are exposed to the interferons in vitro. This resistance was characterized to be non-genetic and dose-dependent, and does not alter other IFN-induced effects such as antiviral effects and elevation of 2',5'-oligoadenylate synthetase activity in IFN-treated cells. The study of these IFN-resistant cells has been extended to an in vivo tumor model. Resistance, if it occurred in vivo, did not adversely affect the survival of IFN-treated mice. Further, IFN-treated mice inoculated with B16 cells that were resistant in vitro (B16 alpha res cells) survived significantly longer than IFN-treated mice inoculated with B16 cells that were sensitive in vitro. The IFN-treated B16 alpha res-inoculated mice had a significantly higher cure rate as well. The prolonged survival of the mice bearing B16 alpha res cell tumors did not seem to be caused by the slower growth rate of the B16 alpha res cells, since experiments performed with a tenfold higher B16 alpha res cell inoculum and a tenfold lower B16 cell inoculum did not show any change in the survival pattern. It is clear that in vitro resistant B16 alpha res cells are more sensitive to antitumor effects induced by IFN in vivo than in vitro sensitive B16 cells.
小鼠B16黑色素瘤细胞在体外暴露于干扰素α（IFNα）和干扰素β（IFNβ）时，会迅速对干扰素的抗增殖作用产生抗性。这种抗性的特点是非遗传性和剂量依赖性的，并且不会改变其他干扰素诱导的效应，如抗病毒效应以及干扰素处理细胞中2',5'-寡腺苷酸合成酶活性的升高。对这些干扰素抗性细胞的研究已扩展到体内肿瘤模型。如果在体内出现抗性，它不会对接受干扰素治疗的小鼠的存活产生不利影响。此外，接种体外抗性B16细胞（B16αres细胞）的干扰素处理小鼠比接种体外敏感B16细胞的干扰素处理小鼠存活时间明显更长。接种B16αres细胞肿瘤的小鼠的延长存活似乎并不是由B16αres细胞生长速度较慢引起的，因为用高十倍的B16αres细胞接种量和低十倍的B16细胞接种量进行的实验并未显示存活模式有任何变化。显然，体外抗性B16αres细胞在体内比体外敏感B16细胞对干扰素诱导的抗肿瘤效应更敏感。
