Study on the possibility of insulin as a carrier of IUdR for hepatocellular carcinoma-targeted therapy.

Aim: 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).

Methods: 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 %.

Results: 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).

Conclusion: It is possible to use insulin as a carrier for carcinoma-targeted therapy mediated by receptor.