Jinno H, Ueda M, Ozawa S, Ikeda T, Enomoto K, Psarras K, Kitajima M, Yamada H, Seno M
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Life Sci. 1996;58(21):1901-8. doi: 10.1016/0024-3205(96)00174-9.
Recombinant human ribonuclease 1 (RNase 1) was chemically linked to recombinant human epidermal growth factor (EGF). The EGF-RNase conjugate showed dose-dependent cytotoxicity for EGF receptor-overexpressing A431 and TE-8 human squamous carcinoma cells with an IC50 of 2 x 10(-7)M and 10(-6)M, respectively, whereas the IC50 of RNase alone was almost 10(-4)M. An unconjugated mixture of EGF and RNase had no greater effect than RNase alone. The conjugate showed no detectable cytotoxicity against EGF receptor-deficient small cell lung cancer cells (H69). Addition of excess EGF in the medium protected A431 cells from the EGF-RNase conjugate cytotoxicity. The cytotoxicity of the EGF-RNase conjugate was positively correlated with the EGF receptor numbers of each cell line. The chimeric toxin composed of only human proteins might be a more useful anti-cancer agent with less immunogenicity than the conventional chimeric toxins.
重组人核糖核酸酶1（RNase 1）与重组人表皮生长因子（EGF）进行化学连接。EGF-RNase偶联物对表皮生长因子受体过表达的A431和TE-8人鳞状癌细胞表现出剂量依赖性细胞毒性，其IC50分别为2×10（-7）M和10（-6）M，而单独的RNase的IC50几乎为10（-4）M。未偶联的EGF和RNase混合物的效果不比单独的RNase更好。该偶联物对表皮生长因子受体缺陷的小细胞肺癌细胞（H69）未表现出可检测到的细胞毒性。在培养基中添加过量的EGF可保护A431细胞免受EGF-RNase偶联物的细胞毒性作用。EGF-RNase偶联物的细胞毒性与各细胞系的表皮生长因子受体数量呈正相关。仅由人蛋白组成的嵌合毒素可能是一种比传统嵌合毒素更有用且免疫原性更低的抗癌剂。
