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Br J Haematol ; 120(3): 396-404, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12580953

RESUMO

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.


Assuntos
Inibidores da Angiogênese/uso terapêutico , NG-Nitroarginina Metil Éster/uso terapêutico , Neovascularização Patológica/tratamento farmacológico , Óxido Nítrico Sintase/antagonistas & inibidores , Plasmocitoma/tratamento farmacológico , Animais , Fatores de Crescimento Endotelial/biossíntese , Feminino , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Linfocinas/biossíntese , Camundongos , Camundongos SCID , Mieloma Múltiplo/patologia , Transplante de Neoplasias , Plasmocitoma/irrigação sanguínea , Plasmocitoma/patologia , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
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