Angiogenesis Inhibition with TNP-470, 2-Methoxyestradiol, and Paclitaxel in Experimental Pancreatic Carcinoma

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Abstract
Inhibition of tumor angiogenesis is a novel therapeutic modality for various malignancies. To investigate the effect of different antiangiogenic agents (TNP-470, 2-methoxyestradiol, and paclitaxel) on growth and neovascularization of experimental pancreatic cancer. In 25 male Lewis rats, tumor induction was achieved by orthotopic and subcutaneous tumor fragment implantation of ductlike pancreatic cancer DSL6A. Four weeks after tumor implantation, the animals were randomly treated with TNP-470, 2-methoxyestradiol, or paclitaxel. After 2 weeks of antiangiogenic therapy, total tumor volume, vital tumor surface, vascular density, and apoptosis were measured. Total tumor volume and vital tumor surface were not significantly different in any of the treatment groups. Similarly, vascular density and apoptosis were not altered by treatment with the various angiogenesis inhibitors at the specific doses used. We conclude that in contrast to many earlier studies, angiogenesis inhibition by a single-drug application and by the doses used in the present model did not reveal a favorable therapeutic effect on pancreatic cancer DSL6A. The combination of different angiogenesis inhibitors or higher doses might be more effective.