Angiogenesis inhibition and cell cycle arrest induced by treatment with Pseudolarix acid B alone or combined with 5-fluorouracil.
Acta Biochim Biophys Sin (Shanghai)
; 44(6): 490-502, 2012 Jun.
Article
en En
| MEDLINE
| ID: mdl-22551583
ABSTRACT
Angiogenesis inhibitors combined with chemotherapeutic drugs have significant efficacy in the treatment of a variety of cancers. Pseudolarix acid B (PAB) is a traditional pregnancy-terminating agent, which has previously been shown to reduce tumor growth and angiogenesis. In this study, we used the high content screening assay to examine the effects of PAB on human umbilical vein endothelial cells (HUVECs). Two hepatocarcinoma 22-transplanted mouse models were used to determine PAB efficacy in combination with 5-fluorouracil (5-Fu). Our results suggested that PAB (0.156-1.250 µM) inhibited HUVECs motility in a concentration-dependent manner without obvious cytotoxicity in vitro. In vivo, PAB (25 mg/kg/day) promoted the anti-tumor efficacy of 5-Fu (5 mg/kg/2 days) in combination therapy, resulting in significantly higher tumor inhibition rates, lower microvessel density values, and prolonged survival times. It was also demonstrated that PAB acted by blocking the cell cycle at both the G(1)/S boundary and M phase, down-regulation of vascular endothelial growth factor, hypoxia-inducible factor 1α and cyclin E expression, and up-regulation of cdc2 expression. These observations provide the first evidence that PAB in combination with 5-Fu may be useful in cancer treatment.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diterpenos
/
Fluorouracilo
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Acta Biochim Biophys Sin (Shanghai)
Asunto de la revista:
BIOFISICA
/
BIOQUIMICA
Año:
2012
Tipo del documento:
Article
País de afiliación:
China