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Modulation of the gamma-secretase activity as a therapy against human hepatocellular carcinoma


1 Department of Microbiology and Immunology, Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Medical School, Southeast University, Nanjing, China
2 Department of Microbiology and Immunology, Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Medical School, Southeast University, Nanjing; Department of Clinical Laboratory Science, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu Province, China
3 Department of Cell Biology, College of Life Science, Beijing Normal University, Beijing, China

Correspondence Address:
Yuqing Shen,
Department of Microbiology and Immunology, Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, Jiangsu Province 210009
China
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Source of Support: None, Conflict of Interest: None

Objective: Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide. The discovery of new therapies against HCC is highly dependable on finding molecules which play essential roles in cancer development. The objective of this study was to evaluate the activity of gamma secretase (g-secretase), and the antitumor effects of a g-secretase inhibitor (GSI) in HCC. Methods: The expression of presenilin 1 (PS1), a core component of g-secretase, was examined by Western blot. Activity of g-secretase was measured by a luciferase-based reporter system, and cancer cells were transfected either with PS1 dominant negative mutant (PS1D385A) or treated with GSI. Results: Expression of PS1 was increased in HCC tissue and several HCC cell lines, which were accompanied by elevated g-secretase activity. Cell colony formation and cell proliferation were decreased upon treatment with GSI but not with PS1D385A transfection. Conclusion: GSIs may be appealing candidates for the development of new therapies against HCC.


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