Delayed hepatocarcinogenesis through antiangiogenic intervention in the nuclear factor-kappa B activation pathway in rats.
Hepatobiliary Pancreat Dis Int
; 9(2): 169-74, 2010 Apr.
Article
en En
| MEDLINE
| ID: mdl-20382589
ABSTRACT
BACKGROUND:
The active form of nuclear factor-kappa B (NF-kappaB) is involved in the initiation, generation, and development of hepatocellular carcinoma (HCC), and is up-regulated in inflammation-associated malignancies. We investigated the dynamic expression of NF-kappaB and its influences on the occurrence of HCC through antiangiogenic (thalidomide) intervention in NF-kappaB activation.METHODS:
Hepatoma models were induced with 2-fluorenylacetamide (2-FAA, 0.05%) in male Sprague-Dawley rats, and thalidomide (100 mg/kg body weight) was administered intragastrically to intervene in NF-kappaB activation. The pathological changes in the liver of sacrificed rats were assessed after hematoxylin and eosin staining. NF-kappaB mRNA was amplified by RT-nested PCR. The alterations of NF-kappaB and vascular endothelial growth factor (VEGF) expression were analyzed by enzyme-linked immunosorbent assay, immunohistochemistry, and Western blotting.RESULTS:
Rat hepatocytes showed denatured, precancerous, and cancerous stages in hepatocarcinogenesis, with an increasing tendency of hepatic NF-kappaB, NF-kappaB mRNA, and VEGF expression, and their values in the HCC group were higher than those in controls (P<0.001). In the thalidomide-treated group, the morphologic changes generated only punctiform denaturation and necrosis at the early or middle stages, and nodular hyperplasia or a little atypical hyperplasia at the final stages, with the expression of NF-kappaB (X2=9.93, P<0.001) and VEGF (X2=8.024, P<0.001) lower than that in the 2-FAA group.CONCLUSION:
NF-kappaB is overexpressed in hepatocarcinogenesis and antiangiogenic treatment down-regulates the expression of NF-kappaB and VEGF, and delays the occurrence of HCC.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
FN-kappa B
/
Inhibidores de la Angiogénesis
/
Neoplasias Hepáticas Experimentales
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Hepatobiliary Pancreat Dis Int
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
China