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Effect of histone acetyltransferase inhibitor against middle ear cholesteatoma in mouse model
Naotaro Akiyama1, Tomomi Yamamoto-Fukuda2, Hiromi Kojima2
1Department of Otorhinolaryngology, Tokyo Dental College Ichikawa General Hospital, Chiba, Japan; Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan.
Objective:
Middle ear cholesteatoma (Cholesteatoma) consists of proliferative epithelial cells. In the previous study, we demonstrated that histone H3 acetylation at lysine 27 (H3K27ac), associated with high transcriptional activation, was accumulated in the Cholesteatoma. In this study, we firstly investigated the expression of H3K27ac and histone acetyltransferase, p300 in human Cholesteatoma tissues. And then, we investigated the effects of a p300 inhibitor, C646, against Cholesteatoma growth.
Methods:
Immunohistochemical analysis was demonstrated in the human Cholesteatoma specimens using anti-p300 and anti-H3K27ac antibodies and in the KGF-induced Cholesteatoma mouse model after p300 inhibitor administration using anti-p300, anti-H3K27ac, and anti-Ki67 antibodies.
Results:
The expression levels of p300 were significantly increased and colocalized with H3K27ac in the human Cholesteatoma specimens. Moreover, C646 decreased proliferative activities of Cholesteatoma cells in the KGF-induced Cholesteatoma mouse model.
Conclusion:
We demonstrated that inhibition of the H3K27ac may be a potential treatment strategy for Cholesteatoma from a new perspective.
