Clercq E D
Cancer Res. 1977 May;37(5):1502-6.
L-929 cells injected s.c. into athymic nude mice cause the formation of single well-defined tumors at the site of inoculation. The development of these tumors is markedly inhibited by polyriboinsinic acid-polyribocytidylic acid [poly(l)-poly(C)], whether poly(l)-poly(C) treatment is initiated one day after L-cell inoculation or 3 weeks later, when tumors have grown to an appreciable size. The antitumor effect of poly(l)-ploy(C) was found to be dose dependent. Multiple injections of 100 microng poly(l)-poly(C) per mouse (congruent to 5 mg/kg) almost completely arrested tumor growth, but even at 1microng/mouse (congruent to 50 microng/kg), poly(l)-poly(C) caused a partial reduction in tumor growth. Mouse interferon administered exogenously in amounts that closely mimicked the interferon blood levels induced endogenously by poly(l)-poly(C) failed to duplicate the antitumor effects of poly(l)-poly(C). Hence, the role of interferon induction in the mechanism of antitumor action of poly(l)-poly(C) can be eliminated. Since all results were obtained with the use of athymic nude mice, the role of thymus-dependent immunity can also be eliminated. At the dosage regimens used to determine the inhibitory effect on L-cell tumor growth, neither poly(L)-poly(C) nor interferon altered the life-span of the nude mice.
将L - 929细胞皮下注射到无胸腺裸鼠体内,会在接种部位形成单个边界清晰的肿瘤。无论在L细胞接种后一天还是3周后(此时肿瘤已生长到可观大小)开始用聚肌苷酸 - 聚胞苷酸[聚(I)-聚(C)]治疗,这些肿瘤的生长都会受到显著抑制。发现聚(I)-聚(C)的抗肿瘤作用具有剂量依赖性。每只小鼠多次注射100微克聚(I)-聚(C)(相当于5毫克/千克)几乎完全抑制肿瘤生长,但即使是每只小鼠1微克(相当于50微克/千克),聚(I)-聚(C)也会使肿瘤生长部分减缓。以与聚(I)-聚(C)内源性诱导产生的干扰素血药浓度相近的量外源性给予小鼠干扰素,未能重现聚(I)-聚(C)的抗肿瘤作用。因此,可以排除干扰素诱导在聚(I)-聚(C)抗肿瘤作用机制中的作用。由于所有结果均是在无胸腺裸鼠身上获得的,胸腺依赖性免疫的作用也可以排除。在用于确定对L细胞肿瘤生长抑制作用的给药方案下,聚(L)-聚(C)和干扰素均未改变裸鼠的寿命。