Inhibition of breast cancer regrowth and pulmonary metastasis in nude mice by anti-gastric ulcer agent, irsogladine.
Irsogladine is a commonly used anti-gastric ulcer agent in Japan, and recent in vivo studies have shown it to have anti-angiogenic properties. The exact role of irsogladine as an inhibitor of angiogenesis remains uncertain. In this study, we show that irsogladine inhibited breast cancer regrowth and pulmonary metastasis but had no anti-angiogenic function against HUVEC cells. Irsogladine failed to inhibit proliferation, tubular formation, and the uPA/MMP-1 mRNA expression of HUVEC cells. We also examined the effect of irsogladine in an orthotopic transplant model of human breast cancer metastasis in athymic mice. Human MDA-MB-435 cells were injected into the mammary fat pads. After 9 weeks, the tumors were resected under general anesthesia. Irsogladine or vehicle was given p.o. daily thereafter. Daily administration of irsogladine at 120 mg/kg per day over a 5-week period had no effect on the body weight of the mice. Tumor regrowth, average volume of pulmonary metastases, and the number of metastases were inhibited by 40, 48 and 64%, respectively. These results suggest that irsogladine may be useful in the breast cancer adjuvant setting.
Nozaki
Shinichi
S
Division of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Maeda
Mitsuaki
M
Tsuda
Hiroyuki
H
Sledge
George W
GW
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology* / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D014183:Transplantation, Heterologous; D014227:Triazines / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D014227:Triazines; C041836:irsogladine