NG-nitro-L-arginine methyl ester inhibits bone metastasis after modified intracardiac injection of human breast cancer cells in a nude mouse model.
We investigated the effects of NG-nitro-L-arginine-methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, on bone metastasis of human breast cancer, MDA-231 cells. Tumor cells (2 x 10(5) cells in 0.2 ml of phosphate-buffered saline; PBS) were injected through the diaphragm into the left ventricle of the heart of laparotomized nude mice (male 5-week-old ICR-nu/nu). L-NAME (2 mg/mouse/injection in 0.1 ml of PBS) was given intraperitoneally to mice 6 h and 3 h before and immediately, 3 h, 6 h, 18 h and 21 h after the intracardiac injection of tumor cells. As a control, 0.1 ml of PBS was injected instead of L-NAME. The effect of NG-nitro-D-arginine-methyl ester (D-NAME; 2 mg/mouse/injection), an inactive analogue of L-NAME, was also investigated to evaluate the specificity of L-NAME action. Radiographical examination 31 days after the tumor-cell injection showed that the incidence and number of osteolytic bone metastases and the number of bones with metastasis in L-NAME-treated mice were significantly reduced compared with those in PBS-treated mice (P < 0.05). The differences between PBS-treated and D-NAME-treated mice were not significant. Our findings suggest that specific and appropriate NOS inhibitors may represent a new pharmacological approach to therapy for cancer patients at risk of developing osteolytic bone metastases.
Iwasaki
T
T
Department of Tumor Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases.
Higashiyama
M
M
Kuriyama
K
K
Sasaki
A
A
Mukai
M
M
Shinkai
K
K
Horai
T
T
Matsuda
H
H
Akedo
H
H
D000818:Animals; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D005260:Female; D006321:Heart; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity*; D011859:Radiography; D013237:Stereoisomerism; D014183:Transplantation, Heterologous; D016042:Transplantation, Heterotopic
D019331:NG-Nitroarginine Methyl Ester