組蛋白去乙醯化酶抑製劑在膀胱癌膀胱灌注治療的協同作用：分子機制與動物模式的初步結果
余家瑩¹、王紹全^{1, 2, 3}、陳文榮^{1, 2, 3}、謝佐宜^{1, 2, 3}、陳順郎^{1, 2, 3}、宋文瑋^{1, 2, 3}
中山醫學大學 ¹醫學系，²醫學研究所；中山醫學大學附設醫院 ³泌尿科
Synergistic effect of histone deacetylase inhibitors in intravesical instillation of bladder cancer: preliminary results of molecular mechanism and animal model
Chia-Ying Yu¹, Shao-Chuan Wang^{1, 2, 3}, Wen-Jung Chen^{1, 2, 3}, Tzuo-Yi Hsieh^{1, 2, 3}, Sung-Lang Chen^{1, 2, 3}, Wen-Wei Sung^{1, 2, 3
1}School of Medicine and ²Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; ³Department of Urology, Chung Shan Medical University Hospital, Taichung, Taiwan

Purpose: Bladder cancer is common malignancy with high tumor recurrence rate. Intravesical instillation of chemotherapy drugs or Bacillus Calmette-Guerin is recommend for preventing tumor recurrence. In bladder cancer, histone deacetylases play the key role in regulation of cell cycle, cell apoptosis, and malignancy which suggests the potential therapeutic role of inhibitors targeting histone deacetylases.

Materials and Methods: In this study, we analyzed the synergistic effect and molecular mechanism of histone deacetylase inhibitors in vitro with MTT, apoptotic, cell cycle assays and caspase activity. The synergistic effect was further confirmed via intravesical instillation in autochthonous rat bladder cancer model (Approval by Chung-Shan Medical University Experimental Animal Center, No. 1920).

Results: Our study evidenced the synergistic effect of histone deacetylase inhibitors combined with chemotherapy drugs with significant increased cell death rate, sub-G1 percentage, caspase activity, and related protein expression. These results were further evidenced with autochthonous rat bladder cancer model under comparison of combination therapy to the chemotherapy along which showed less tumor growth in the combination group.

Conclusions: Our preliminary results observed the therapeutic role of histone deacetylase inhibitors in intravesical instillation treatment for bladder cancer which might provide new insights to current therapy.