CC-5079: a small molecule with MKP1, antiangiogenic, and antitumor activity.
J Surg Res
; 164(1): 116-25, 2010 Nov.
Article
em En
| MEDLINE
| ID: mdl-19726061
ABSTRACT
INTRODUCTION:
CC-5079, a small molecule inhibitor of tubulin polymerization and phosphodiesterase-4 activity, was evaluated for antiangiogenic and antitumor activities. MATERIALS ANDMETHODS:
First, CC-5079 in vitro activity on human umbilical vein endothelial cells (HUVECs), fibroblasts, and MC38 were evaluated by proliferation, migration, and invasion assays. Second, CC-5079 effect on microvessel formation was evaluated ex vivo by chick chorioallantoic membrane (CAM), rat aortic rings assays, and with directed in vivo angiogenesis assay (DIVAA). Third, CC-5079 antitumor effect was determined in treatment of C57BL/6 mice with MC38 tumors. Finally, CC-5079 modulation of MKP1 in HUVECs, human fibroblast, and MC38 were determined by RNA isolation for qRT-PCR.RESULTS:
At the 0.1 µM concentration CC-5079 significantly inhibited HUVEC, fibroblast, and MC38 proliferation and migration (all P < 0.001). At the 0.1 µM concentration, CC-5079 also inhibited HUVEC invasion (P < 0.05) but not fibroblast. In the CAM and rat aortic ring assays, CC-5079 at 0.1 µM inhibited microvessel formation (P < 0.05). By DIVAA, CC-5079 at 1 mg/kg/d continuous delivered inhibited microvessel formation (P < 0.05). Intraperitoneal CC-5079 was well tolerated and inhibited the growth of subcutaneous MC38 at 100 mg/kg/d (P < 0.01). By qRT-PCR, CC-5079 stimulated MKP1 expression in HUVEC and fibroblast.CONCLUSION:
CC-5079 demonstrated stimulation of MKP1, antiangiogenic, and antitumor properties.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Colo
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Inibidores da Angiogênese
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Fosfatase 1 de Especificidade Dupla
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Antineoplásicos
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Nitrilas
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Surg Res
Ano de publicação:
2010
Tipo de documento:
Article