Abstract
Background: Vascular disrupting agents (VDAs) are designed to cause a rapid and selective shutdown of the established tumor vasculature, which leads to secondary ischemic tumor cell death. Materials and Methods: We examined the efficacy of a novel VDA, MN-029, in the rodent KHT sarcoma model. Results: A significant reduction in the functional vessel number was observed after intraperitoneal injection of MN-029 at a dose of 100 mg/kg. Histological evaluation showed extensive necrosis (~90%) by 24 h. MN-029 treatment to the tumor-bearing mice also resulted in a dose-dependent tumor cell killing. When used in combination with radiation or cisplatin chemotherapy, a 100 mg/kg dose of MN-029 significantly enhanced tumor killing compared to that seen with radiation or cisplatin alone. Conclusion: The results demonstrated that MN-029 could cause rapid vascular shutdown in solid tumors, dose-dependent secondary tumor cell killing, and effective enhancement of the antitumor effects of radiation and cisplatin chemotherapy.
Footnotes
- Received July 6, 2005.
- Accepted July 15, 2005.
- Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved