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Delayed hepatocarcinogenesis through antiangiogenic intervention in the nuclear factor-kappa B activation pathway in rats |
Zhi-Zhen Dong, Deng-Fu Yao, Wei Wu, Min Yao, Hong-Bo Yu, Jun-Jun Shen, Li-Wei Qiu, Ning-Hua Yao, Wen-Li Sai and Jun-Ling Yang |
Nantong, China
Author Affiliations: Department of Diagnostics, Medical College (Dong ZZ), Research Center of Clinical Medicine (Yao DF, Wu W, Qiu LW, Sai WL and Yang JL), Department of Laboratory Science (Yao M), and Department of Oncology (Shen JJ and Yao NH), Affiliated Hospital of Nantong University, Nantong 226001, China; Department of Chemotherapy, Nantong Cancer Hospital, Nantong 226007, China (Yu HB)
Corresponding Author: Deng-Fu Yao, MD, PhD, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China (Tel: 86-513-85052413; Fax: 86-513-85052523; Email: yaodf@ahnmc.com) |
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Abstract BACKGROUND: The active form of nuclear factor-kappa B (NF-κB) 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-κB and its influences on the occurrence of HCC through antiangiogenic (thalidomide) intervention in NF-κB 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-κB activation. The pathological changes in the liver of sacrificed rats were assessed after hematoxylin and eosin staining. NF-κB mRNA was amplified by RT-nested PCR. The alterations of NF-κB 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-κB, NF-κB 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-κB (χ2=9.93, P<0.001) and VEGF (χ2=8.024, P<0.001) lower than that in the 2-FAA group.
CONCLUSION: NF-κB is overexpressed in hepatocarcinogenesis and antiangiogenic treatment down-regulates the expression of NF-κB and VEGF, and delays the occurrence of HCC.
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Cite this article: |
Dong ZZ,
Yao DF,
Wu W,
et al.
Delayed hepatocarcinogenesis through antiangiogenic intervention in the nuclear factor-kappa B activation pathway in rats.
Hepatobiliary Pancreat Dis Int
2010;
9(2):
169-174. DOI:
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URL: |
http://dx.doi.org/ OR http://www.hbpdint.com/EN/Y2010/V9/I2/169 |
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