title: Inhibitory effect of the angiogenesis inhibitor TNP-470 on tumor growth and metastasis in nude mice bearing human hepatocellular carcinoma.
abstract: The antitumor and anti-metastatic effects of a potent angiogenesis inhibitor, O-(chloroacetyl-carbamoyl)fumagillol (TNP-470), was investigated in a highly metastatic model of human hepatocellular carcinoma-LCI-D20. Small pieces of LCI-D20 tumor tissue were implanted subcutaneously into the right axillary region of 24 nude mice; the mice were then randomized into two groups. To one group, TNP-470 30 mg/kg was given as a subcutaneous injection every other day from day 1 to day 15 and the mice were sacrificed on day 26. An antitumor effect of TNP-470 was clearly demonstrated by tumor weight (0.97 +/- 0.34 g compared to 2.04 +/- 0.34 g, P < 0.001) and alpha-Fetoprotein value (93 +/- 59 micrograms/L compared to 769 +/- 282 micrograms/L, P < 0.001). There was also an anti-metastatic effect of TNP-470. Lung metastases developed in only 1 of 12 mice in the treated group, while they developed in 6 of mice of the control group. No severe side-effect of TNP-470 was found in this study. In vitro study revealed that the purified hepatoma cells were insensitive to TNP-470 (the 50% inhibitory concentration was 43 micrograms/ml). These results suggest that the angiogenesis inhibitor TNP-470 has both strong antitumor and anti-metastatic effects on a human hepatocellular carcinoma model in nude mice.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Shanghai Medical University, People's Republic of China.
authors.forename: J L
authors.initials: JL
authors.lastname: Xia
authors.forename: B H
authors.initials: BH
authors.lastname: Yang
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Tang
authors.forename: F X
authors.initials: FX
authors.lastname: Sun
authors.forename: Q
authors.initials: Q
authors.lastname: Xue
authors.forename: D M
authors.initials: DM
authors.lastname: Gao
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D003510:Cyclohexanes; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol