A14^(125)I-胰岛素与H_(22)肝癌细胞胰岛素受体结合的研究

目的 体外分析H2 2 肝癌细胞与正常肝细胞膜的胰岛素受体表达 ,探讨胰岛素作为受体介导靶向治疗载体的可行性及临床应用前景。方法 用氯氨T法制备A14 12 5I 胰岛素 ,电泳分离纯化标记物并用自身置换比放射性测定和过量受体结合实验法鉴定标记物质量 ,再制备H2 2 肝癌细胞及正常小鼠肝细胞 ,进行体外受体结合实验 ,分别测定12 5I 胰岛素与小鼠H2 2 肝癌及正常肝细胞膜胰岛素受体结合的Kd值及Bmax值以及其竞争结合曲线。12 5I 胰岛素受体结合的Kd值及Bmax值用t检验分析 ,饱和结合曲线用Scatchard分析。结果 小鼠H2 2 肝癌细胞及正常小鼠肝细胞胰岛素受体Bmax值分别为 (5 .6± 1.1) pmol/10 6细胞和 (3 .2± 0 .8) pmol/10 6细胞 ,高亲和力Kd值为 (1.8± 0 .6)nmol/L及 (2 .1± 0 .9)nmol/L ,低亲和力Kd值为 (3 2 .0± 10 .7)nmol/L及 (3 7.0± 12 .3 )nmol/L。癌细胞胰岛素受体Bmax值明显高于正常肝细胞 (P<0 .0 5 )。受体结合实验表明 ,12 5I 胰岛素与H2 2 肝癌及正常细胞的结合具有特异性。结论 12 5I 胰岛素与H2 2 肝癌及正常小鼠肝细胞膜受体的结合具有高度特异性 ,H2 2 肝癌细胞较正常小鼠肝细胞表达胰岛素受体增加 ,提示胰岛素可作为抗癌载体通过与肝癌细胞表面受体结合而介导肝癌的靶向治疗。

Reactivation of the insulin-like growth factor-Ⅱsignaling pathway in human hepatocellular carcinoma

Constitutive activation of the insulin-like growth factor (IGF)-signaling axis is frequently observed in human hepatocellular carcinoma(HCC).Especially the over- expression of the fetal growth factor IGF-Ⅱ,IGF-Ⅰ receptor(IGF-IR),and cytoplasmic downstream effectors such as insulin-receptor substrates(IRS)contribute to proliferation,anti-apoptosis,and invasive behavior. This review focuses on the relevant alterations in this signaling pathway and independent in vivo models that support the central role IGF-Ⅱsignaling during HCC development and progression.Since this pathway has become the center of interest as a target for potential anti-cancer therapy in many types of malignancies,various experimental strategies have been developed,including neutralizing antibodies and selective receptor kinase inhibitors,with respect to the specific and efficient reduction of oncogenic IGF-Ⅱ/IGF-IR-signaling.