Arnold L J, Dagan A, Gutheil J, Kaplan N O
Proc Natl Acad Sci U S A. 1979 Jul;76(7):3246-50. doi: 10.1073/pnas.76.7.3246.
We have found that poly(L-lysine) can be a very effective agent in preventing the growth of Ehrlich ascites tumors in mice. When given optimal doses of poly(L-lysine) (Mr 60 x 10(3)) intraperitoneally for 5 consecutive days, beginning on day 1 after inoculation with Ehrlich ascites cells. White Swiss mice show nearly a 100% remission from subsequent tumor growth. Rechallenge of "cured" animals with tumor cells, however shows no long-term immunological protection. In tissue culture, poly(L-lysine) shows a related potent cytotoxicity with HeLa cells; interestingly, the D isomer. In addition, there is a strong molecular weight dependence in that the small polylysine (Mr 3 x 10(3)) possesses less than 1/20th the cytotoxicity of large polymers (Mr 70 x 10(3)) on a weight basis in both cell culture and animal studies. At the same time, none of these lysine polymers gives any significant increase in life span to BDF1 mice infected with L1210 murine leukemia cells. We have also further explored the mechanism by which the polylysines express their cytotoxicity. These data indicate that lysine polymers show cell specificity in their action and in some cases they may be beneficial as potent antineoplastic agents, particularly when molecular weight is taken into consideration.
我们发现聚（L-赖氨酸）可以成为预防小鼠艾氏腹水瘤生长的非常有效的药物。从接种艾氏腹水细胞后的第1天开始，连续5天腹腔注射最佳剂量的聚（L-赖氨酸）（分子量60×10³）。瑞士白化小鼠显示出后续肿瘤生长几乎100%的缓解。然而，用肿瘤细胞对“治愈”的动物进行再次攻击，并未显示出长期的免疫保护作用。在组织培养中，聚（L-赖氨酸）对HeLa细胞显示出相关的强细胞毒性；有趣的是，D异构体。此外，存在很强的分子量依赖性，即在细胞培养和动物研究中，小聚赖氨酸（分子量3×10³）在重量基础上的细胞毒性不到大聚合物（分子量70×10³）的1/20。同时，这些赖氨酸聚合物对感染L1210小鼠白血病细胞的BDF1小鼠的寿命没有任何显著延长。我们还进一步探索了聚赖氨酸发挥其细胞毒性的机制。这些数据表明赖氨酸聚合物在其作用中表现出细胞特异性，在某些情况下，它们作为有效的抗肿瘤药物可能是有益的，特别是在考虑分子量时。
