Abnormal expression of insulin-like growth factor-I receptor in hepatoma tissue and its inhibition to promote apoptosis of tumor cells.

Abnormal signaling of insulin-like growth factor I receptor (IGF-IR) is associated with hepatocellular carcinoma, but the underlying molecular mechanisms remain largely unknown. The objective of this study was to investigate IGF-IR's role as a signaling molecule, its pathological alteration in hepatoma tissues, and its effect on hepatoma cell proliferation when inhibited. As measured by immunohistochemical analysis, the incidence of hepatic IGF-IR expression in cancerous tissue was 80.0 % (24 of 30), which was significantly higher (P < 0.05) than 43.3 % (13 of 30) occurrence in the surrounding tissue and the nondetectable (0 of 30) frequency in the distal cancerous tissue. Hepatoma IGF-IR expression was correlated to the differentiation degree and not to the number or size of tumors, HBV infection, and AFP level. The in vitro IGF-IR expression in hepatoma cells was down-regulated significantly by picropodophyllin, a specific kinase inhibitor, in a time- and dose-dependent manner. Cell proliferation was inhibited through typical mechanisms of promoting apoptosis and cell cycle arrest (G2/M phase). Up-regulation of IGF-IR in hepatocarcinogenesis suggests that the down-regulation of IGF-IR expression could be a specific molecular target for hepatoma cell proliferation.