ANTIPROLIFERATIVE EFFECTS OF TNP-470 ON HUMAN-MALIGNANT GLIOMA IN-VIVO - POTENT INHIBITION OF TUMOR ANGIOGENESIS

A novel angiogenesis inhibitor TNP-470 was investigated for its anti-t umor activity against malignant gliomas both in vitro and in vivo. TNP -470 cytostatically inhibited the growth in all of the seven glioma ce ll lines in culture including anticancer drug resistant cells. The 50% inhibitory concentrations (IC50) of these glioma cell lines were 10 t o 30 mu g/ml and they were 10 to 20 times higher than IC50 of normal e ndothelial cells. TNP-470 (30 mg/kg, i.p., every other day) also signi ficantly inhibited the tumor growth of T98G-transplanted nude mice. Mi croscopically, tumor vessels after the treatment of the tumor-bearing mice with TNP-470 became fewer in number and smaller in diameter than those without treatment. Furthermore, there appeared extensive necroti c areas in the tumor with TNP-470. These results indicate that TNP-470 is a potent angiogenesis inhibitor for malignant gliomas. In addition , the studies of labeling index of BrdU and Ki67 suggest that TNP-470 may act mainly on tumor endothelial cells, thus resulting in reduction of the tumor growth.