Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan, ROC.
Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan, ROC.
Cancer Lett. 2014 Apr 28;346(1):84-93. doi: 10.1016/j.canlet.2013.12.016. Epub 2013 Dec 16.
Many histone deacetylase (HDAC) inhibitors show limited therapeutic effects for solid tumors. Here, we develop a novel HDAC inhibitor YCW1 and verify the combination effect of YCW1 and cisplatin in lung cancer pre-clinical models. YCW1 exerted cancer-specific cytotoxicity via mitochondria-mediated apoptosis. YCW1 and cisplatin showed synergistic anti-tumor effects through impairment of DNA damage repair. YCW1 inhibited tumor growth in lung orthotopic and subcutaneously implanted xenograft models. YCW1 significantly suppressed lung metastases via inhibition of focal adhesion complex. Our findings suggested that YCW1 is a potential HDAC inhibitor for lung cancer treatment as single and in combination regimens with cisplatin.
许多组蛋白去乙酰化酶（HDAC）抑制剂对实体瘤的治疗效果有限。在这里，我们开发了一种新型的 HDAC 抑制剂 YCW1，并在肺癌临床前模型中验证了 YCW1 与顺铂的联合效应。YCW1 通过线粒体介导的细胞凋亡发挥肿瘤特异性细胞毒性。YCW1 和顺铂通过损害 DNA 损伤修复显示出协同的抗肿瘤作用。YCW1 抑制了肺癌原位和皮下移植瘤模型中的肿瘤生长。YCW1 通过抑制粘着斑复合物显著抑制肺转移。我们的研究结果表明，YCW1 是一种有潜力的用于肺癌治疗的 HDAC 抑制剂，无论是单独使用还是与顺铂联合使用。
