Effect of sodium arsenite on Caveolin-1, eNOS, IKKβand COX-2 expression in SV-40 immortalized humanuroepithelial cells and urothelial carcinomas
| Autor: | Xuan-Ping Liu, 劉萱蘋 |
|---|---|
| Rok vydání: | 2009 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 97 Purpose: Arsenic is a known human carcinogen, and extend to every part of the earth''s crust. Cancer risk assessments have been based on epidemiological studies of a large population exposed to arsenic in south western Taiwan. It is well known that there was significantly correlation between urothelial cancer and blackfoot disease with arsenic. Arsenic exposure can accumulate in the liver, spleen, kidneys, and gastrointestinal tract, further result in the development of various cancers. Caveolin-1 scaffolding domain bind to eNOS and thereby inhibit NO production. NO represses IKK through S-nitrosylation in the immune system. IKK-mediated NF-κB activation can upregulate COX-2 expression in oncogenesis. The aim of this study is to determine if sodium arsenite can affect Caveolin-1 and downstream signaling molecules expression(eNOS, IKKβ and COX-2) in low dose condition. In addition, we also performed immunohistochemistry staining of Caveolin-1, eNOS, IKKβ and COX-2 in human urothelial carcinoma specimens in both the blackfoot disease and non-blackfoot disease endemic areas in Taiwan. Material and method: SVHUC-1 cells were treated in culture with low concentration sodium arsenite. The expression of Caveolin-1, eNOS, IKKβ and COX-2 were examined by Immunocytochemistry and western blotting. Furthermore, we collected 34 paraffin-embedded specimens of urothelial carcinoma with blackfoot disease and non blackfoot disease areas. The sections were examined immunohistochemistry for Caveolin-1, eNOS, IKKβ and COX-2 expression. The correlations with clinicopathologic features were evaluated statistically. Results: Immunocytochemical staining and Western blotting results revealed increased expression of Caveolin-1, IKKβ and COX-2 and decreased eNOS in low concentration of arsenite treated SV-HUC-1 cells. Our findings indicate that U0126 inhibitor significantly attenuated arsenite-induced expression of Caveolin-1, IKKβ and COX-2, and restored the reduced eNOS expression. Immunohistochemistry staining revealed cytoplasmic higher expression of Caveolin-1, IKKβ and COX-2 in patients with urothelial carcinoma blackfoot disease(P=0.037, P=0.01, P=0.0001), but decrease of eNOS expression in blackfoot disease endemic area(P=0.0001). Conclusion: Our present result provide new aspects for the correlation among Caveolin-1 and downstream signaling molecules expression, which may play important roles in the mechanisms of arsenic-induced urothelial carcinogenesis. By U0126 inhibitor treatment, we found the inhibitor could be a potentially therapeutic agent for urothelial cancer. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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