Ou Xiao-Hong, Kuang An-Ren, Peng Xian, Zhong Yu-Guo
Department of Nuclear Medicine, West China Hospital of Sichuan University, China.
World J Gastroenterol. 2003 Aug;9(8):1675-8. doi: 10.3748/wjg.v9.i8.1675.
To evaluate the possibility of using insulin as a carrier for carcinoma-targeted therapy mediated by receptor, and to investigate the expression of insulin receptor in human hepatocellular carcinoma and the receptor binding characteristics of insulin-IUdR (iododeoxyuridine).
IUdR was covalently conjugated to insulin. Receptor binding assays of (125)I-insulin to human hepatocellular carcinoma and its adjacent tissue were performed. Competitive displacements of (125)I-insulin by insulin and insulin-IUdR to bind to insulin receptor were respectively carried out. Statistical comparisons between the means were made with paired t-test at a confidence level of 95 %.
The data indicated that there were high- and low- affinity binding sites for (125)I-insulin on both hepatocellular carcinoma and its adjacent tissue. Hepatocellular carcinoma had a significantly higher Bmax for high affinity binding site than its adjacent liver tissue (P<0.05, t=2.275). Insulin-IUdR competed as effectively as insulin with (125)I-insulin for binding to insulin receptor. Values of IC(50)1, C(50)2, KI1 and KI2 for insulin-IUdR were 11.50+/-2.83 nmol x L(-1), 19.35+/-5.11 nmol x L(-1), 11.26+/-2.65 nmol x L(-1) and 19.30+/-5.02 nmol x L(-1) respectively, and for insulin were 5.01+/-1.24 nmol x L(-1),17.75+/-4.86 nmol x L(-1), 4.85+/-1.12 nmol x L(-1) and 17.69+/-4.81 nmol x L(-1), respectively. Values of IC(50)1 and KI1 for insulin-IUdR were significantly higher than that for insulin (P<0.01, t=4.537 and 4.813).
It is possible to use insulin as a carrier for carcinoma-targeted therapy mediated by receptor.
评估胰岛素作为受体介导的癌靶向治疗载体的可能性，并研究胰岛素受体在人肝细胞癌中的表达以及胰岛素 - 碘脱氧尿苷（IUdR）的受体结合特性。
将IUdR与胰岛素共价结合。进行了¹²⁵I - 胰岛素与人肝细胞癌及其邻近组织的受体结合试验。分别进行了胰岛素和胰岛素 - IUdR对¹²⁵I - 胰岛素结合胰岛素受体的竞争性置换。采用配对t检验在95%置信水平下对均值进行统计学比较。
数据表明，肝细胞癌及其邻近组织上均存在¹²⁵I - 胰岛素的高亲和力和低亲和力结合位点。肝细胞癌高亲和力结合位点的Bmax显著高于其邻近肝组织（P<0.05，t = 2.275）。胰岛素 - IUdR与胰岛素一样有效地与¹²⁵I - 胰岛素竞争结合胰岛素受体。胰岛素 - IUdR的IC₅₀₁、C₅₀₂、KI₁和KI₂值分别为11.50±2.83 nmol·L⁻¹、19.35±5.11 nmol·L⁻¹、11.26±2.65 nmol·L⁻¹和19.30±5.02 nmol·L⁻¹，胰岛素的相应值分别为5.01±1.24 nmol·L⁻¹、17.75±4.86 nmol·L⁻¹、4.85±1.12 nmol·L⁻¹和17.69±4.81 nmol·L⁻¹。胰岛素 - IUdR的IC₅₀₁和KI₁值显著高于胰岛素（P<0.01，t = 4.537和4.813）。
胰岛素有可能作为受体介导的癌靶向治疗载体。
