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 Wang1, 2, 3, Wen-Jung Chen1, 2, 3, Tzuo-Yi Hsieh1, 2, 3, Sung-Lang Chen1, 2, 3, Wen-Wei Sung1, 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.

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    發表人
    TUA人資客服組
    單位
    台灣泌尿科醫學會
    建立
    2019-06-28 23:00:09
    最近修訂
    2019-07-04 15:25:45
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