Preclinical studies of the novel vascular disrupting agent MN-029.
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.


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 (approximately 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.


CONCLUSIONS
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.
Shi
Wenyin
W
Department of Radiation Oncology, Shands Cancer Center, University of Florida, Gainesville, FL 32610, USA.
Siemann
Dietmar W
DW
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D008809:Mice, Inbred C3H; D009336:Necrosis; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D012513:Sarcoma, Experimental / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy
D020533:Angiogenesis Inhibitors; D001562:Benzimidazoles; C506648:denibulin