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

Teruo Iwasaki, Masahiko Higashiyama, Keiko Kuriyama, Akira Sasaki, Mutsuko Mukai, Kiyoko Shinkai, Takeshi Horai, Hikaru Matsuda, Hitoshi Akedo

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

We investigated the effects of N(G)-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 105 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 N(G)-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.

Original languageEnglish
Pages (from-to)861-866
Number of pages6
JournalJapanese Journal of Cancer Research
Volume88
Issue number9
DOIs
Publication statusPublished - Sep 1997

Keywords

  • Bone metastasis
  • Human breast cancer
  • N(G)-nitro-L-arginine methyl ester (L-NAME)
  • Nitric oxide (NO)
  • Nude-mouse model

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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