Discovery of a novel HDACi structure that inhibits the proliferation of ovarian cancer cells in vivo and in vitro

发现一种新型HDACi结构,可在体内和体外抑制卵巢癌细胞增殖

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作者:Miao Bai, Mengqi Cui, Mingyue Li, Xinlei Yao, Yulun Wu, Lihua Zheng, Luguo Sun, Qiuhang Song, Shuyue Wang, Lei Liu, Chunlei Yu, Yanxin Huang

Abstract

Histone deacetylases (HDACs) exhibit increased expression in cancer and promote oncogenesis via the acetylation of or interactions with key transcriptional regulators. HDAC inhibitors (HDACis) decrease HDAC activity to selectively inhibit the occurrence and development of tumors. Our study screened and obtained a new HDACi structure. In vitro experiments have showed that among the leads, Z31216525 significantly inhibited the proliferation and induced the apoptosis of epithelial ovarian cancer (EOC) cells. In vivo experiments demonstrated that compared to the control, Z31216525 significantly inhibited tumor growth and showed very low toxicity. Further mechanistic studies revealed that Z31216525 may exert an antitumor effect by inhibiting the expression of the c-Myc gene. Collectively, our studies identified a novel HDACi that is expected to become a new potential therapeutic drug for EOC and has important value for the design of new HDACi structures.

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