Summary
A novel angiogenesis inhibitor TNP-470 was investigated for its anti-tumor activity against malignant gliomas bothin vitro andin vivo. TNP-470 cytostatically inhibited the growth in all of the seven glioma cell lines in culture including anticancer drug resistant cells. The 50% inhibitory concentrations (IC50) of these glioma cell lines were 10 to 30 Μg/ml and they were 10 to 20 times higher than IC50 of normal endothelial cells. TNP-470 (30 mg/kg, i.p., every other day) also significantly inhibited the tumor growth of T98G-transplanted nude mice. Microscopically, 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 necrotic 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.
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Taki, T., Ohnishi, T., Arita, N. et al. Anti-proliferative effects of TNP-470 on human malignant gliomain vivo: potent inhibition of tumor angiogenesis. J Neuro-Oncol 19, 251–258 (1994). https://doi.org/10.1007/BF01053279
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DOI: https://doi.org/10.1007/BF01053279