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 α-Fetoprotein value (93±59 μg/L compared to 769±282 μg/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 μg/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.
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Abbreviations
- TNP-470:
-
O-(chloroacetyl-carbamoyl) Fumagillol
- MTT :
-
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
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This work was partly supported by the CHina Medical Board of New York, grant 93-583, and a Leading Speciality grant of Shanghai Health Bureau
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Xia, JL., Yang, BH., Tang, ZY. et al. Inhibitory effect of the angiogenesis inhibitor TNP-470 on tumor growth and metastasis in nude mice bearing human hepatocellular carcinoma. J Cancer Res Clin Oncol 123, 383–387 (1997). https://doi.org/10.1007/BF01240121
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DOI: https://doi.org/10.1007/BF01240121