A nitric oxide synthase inhibitor, NG -nitro-l -arginine-methyl-ester, exerts potent antiangiogenic effects on plasmacytoma in a newly established multiple myeloma severe combined immunodeficient mouse model
| Autor: | Fumihiko Matsuno, Hiromitsu Matsuzaki, Yumi Mitsuya, Naoko Harada, Hiroyuki Hata, Akitoshi Nagasaki, Hiroaki Mitsuya, Shima Uneda |
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| Rok vydání: | 2003 |
| Předmět: |
Vascular Endothelial Growth Factor A
Melphalan medicine.medical_specialty Angiogenesis Angiogenesis Inhibitors Endothelial Growth Factors Mice SCID Biology Metastasis Mice chemistry.chemical_compound Internal medicine Tumor Cells Cultured medicine Animals Doxorubicin Lymphokines Neovascularization Pathologic Vascular Endothelial Growth Factors Hematology medicine.disease Nitric oxide synthase NG-Nitroarginine Methyl Ester Endocrinology Paclitaxel chemistry Cell culture biology.protein Cancer research Intercellular Signaling Peptides and Proteins Plasmacytoma Female Nitric Oxide Synthase Multiple Myeloma Neoplasm Transplantation medicine.drug |
| Zdroj: | British Journal of Haematology. 120:396-404 |
| ISSN: | 0007-1048 |
| Popis: | Angiogenesis is one of critical factors in sustaining the growth, invasion and metastasis of certain solid tumours and haematological malignancies such as multiple myeloma (MM). In the present study, we examined the anticancer potential of an inhibitor of nitric oxide synthase (NOS), NG-nitro-l-arginine methyl ester (L-NAME), in a novel severe combined immunodeficient mouse model (KHM mouse) that harbours the highly sanguineous plasmacytoma cell line KHM-4, derived from a patient with highly chemoresistant MM. KHM mice were intraperitoneally administered with either L-NAME, doxorubicin, melphalan, or paclitaxel. A significant reduction in tumour sizes was noted in L-NAME-administered KHM mice while no significant reduction was observed in melphalan- or doxorubicin-administered mice. A profound decrease in angiogenesis was observed in tumour tissues from L-NAME- and paclitaxel-administered KHM mice. A marked decrease in human vascular endothelial cell growth factor (VEGF) levels was identified in tumour tissues from L-NAME-administered KHM mice, strongly suggesting that L-NAME suppressed VEGF production by tumour cells through its inhibition of NOS in tumour cells, resulting in reduced neovasculization in mice leading to the regression of tumour sizes. The present data represent the first observations that certain NOS inhibitors potentially serve as experimental agents for the treatment of chemoresistant MM and plasmacytoma. |
| Databáze: | OpenAIRE |
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