Mechanism of interferon alpha on inhibition of metastasis and angiogenesis of hepatocellular carcinoma after curative resection in nude mice

The aim of this study was to examine the mechanism of interferon alpha (IFN-α) on inhibition of metastasis and recurrence of hepatocellular carcinoma (HCC). Nude mice bearing human HCC xenografts with high metastatic potential (LCI-D20) underwent curative resection of tumors on postimplant day 11. IFN-α was begun the next day at different dosages given subcutaneously for 35 consecutive days; normal saline solution was injected into the control mice. The mice were killed 48 hours after the final treatment, and the parameters were evaluated. The HCC intrahepatic recurrence rate, the size of the recurrent lesions, the rate of lung metastasis, the serum vascular endothelial growth factor level, and the microvessel density (immunohistochemistry) were as follows: 100%, 2136 ± 794 mm³ (mean ± standard deviation), 100%, 265.7 ± 154.7 pg/ml, and 144 ± 37/HP, respectively, in the control mice, whereas these same values were 62.5%, 89 ± 45 mm³, 12.5%, 53.3 ± 9.9 pg/ml, and 86 ± 25/HP, respectively, in the IFN-α 1.5 × 10⁷ U/kg treatment group (P < 0.05) and 26.7%, 46 ± 21 mm³, 0%, 65.2 ± 17.9 pg/ml, and 39 ± 14/HP in the IFN-α 3 × 10⁷ U/kg treatment group, respectively (P < 0.05). However, a significant difference was not found in the serum levels of basic fibroblast growth factor among the control and IFN-α treatment groups. IFN-α inhibits metastasis and recurrence of human HCC after curative resection in nude mice mediated by antiangiogenesis through downregulating expression of vascular endothelial growth factor but not basic fibroblast growth factor. Winner of the 2002 Grassi Prize, International Society of Digestive Surgery, Hong Kong, China, December 11, 2002. Supported in part by State Key Basic Research Program Grant G1998051211, National Natural Scientific Foundation of China 30100077, and Fudan Scientific Foundation.