NG-nitro-L-arginine methyl ester inhibits bone metastasis after modified intracardiac injection of human breast cancer cells in a nude mouse model - PubMed (original) (raw)

NG-nitro-L-arginine methyl ester inhibits bone metastasis after modified intracardiac injection of human breast cancer cells in a nude mouse model

T Iwasaki et al. Jpn J Cancer Res. 1997 Sep.

Abstract

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.

PubMed Disclaimer

Similar articles

Cited by

References

    1. ) Orr , F. W. , Sanchez‐Sweatman , O. H. , Kostenuik , P. and Singh , G.Tumor‐bone interactions in skeletal metastasis . Clin. Orthop. , 312 , 19 – 23 ( 1995. ). - PubMed
    1. ) Yoneda , T. , Sasaki , A. and Mundy , G. R.Osteolytic bone metastasis in breast cancer . Breast Cancer Res. Treat. , 32 , 73 – 84 ( 1994. ). - PubMed
    1. ) Moncada , S. , Palmer , R. M. J. and Higgs , E. A.Nitric oxide: physiology, pathophysiology and pharmacology . Pharmacol. Rev. , 43 , 109 – 142 ( 1991. ). - PubMed
    1. ) Andrade , S. P. , Hart , I. R. and Piper , P. J.Inhibitors of nitric oxide synthase selectively reduce flow in tumour‐associated neovasculature . Br. J. Pharmacol. , 107 , 1092 – 1095 ( 1992. ). - PMC - PubMed
    1. ) Jenkins , D. C. , Charles , I. G. , Thomsen , L. L. , Moss , D. W. , Holmes , L. S. , Baylis , S. A. , Rhodes , P. , Westmore , K. , Emson , P. C. and Moncada , S.Roles of nitric oxide in tumor growth . Proc. Natl. Acad. Sci. USA , 92 , 4392 – 4396 ( 1995. ). - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources