Antitumor effects of angiogenesis inhibitor 0-(chloroacetyl-carbamoyl) fumagillol (TNP-470) against murine renal cell carcinoma.

Abstract

The effect of 0-(chloroacetyl-carbamoyl) fumagillol (TNP-470) on tumor growth and metastasis is investigated. BALB/c mice were inoculated with Renca murine tumor and graded doses of TNP-470 were given subcutaneously every other day beginning on day 1 and ending on day 9. Tumor angiogenesis was measured quantitatively by a colorimetric assay. TNP-470 inhibited tumor growth and prolonged the life span of Renca-bearing mice in a dose-dependent manner. Body weight-loss was not observed in the mice given less than 30 mg./kg./day. When the treatment was delayed on day 6, TNP-470 did not inhibit tumor growth, pointing to the importance of the timing of drug administration in relation to disease stage. Tumor angiogenesis was inhibited 33 to 62% of the control level by TNP-470. Furthermore, TNP-470 reduced pulmonary and hepatic metastatic foci of intravenously inoculated Renca and of the tumor inoculated in the spleen. These data suggest that TNP-470 may be effective as a treatment of renal cell carcinoma, especially when micrometastases are involved.