Published online Aug 15, 2003. doi: 10.3748/wjg.v9.i8.1675
Revised: January 16, 2003
Accepted: February 17, 2003
Published online: August 15, 2003
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 125I-insulin to human hepatocellular carcinoma and its adjacent tissue were performed. Competitive displacements of 125I-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 125I-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 125I-insulin for binding to insulin receptor. Values of IC501, C502, KI1 and KI2 for insulin-IUdR were 11.50 ± 2.83 nmol·L-1, 19.35 ± 5.11 nmol·L-1, 11.26 ± 2.65 nmol·L-1 and 19.30 ± 5.02 nmol·L-1 respectively, and for insulin were 5.01 ± 1.24 nmol·L-1,17.75 ± 4.86 nmol·L-1, 4.85 ± 1.12 nmol·L-1 and 17.69 ± 4.81 nmol·L-1, respectively. Values of IC501 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.