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

被引:12
|
作者
Bai, Miao [1 ]
Cui, Mengqi [1 ]
Li, Mingyue [1 ]
Yao, Xinlei [1 ]
Wu, Yulun [1 ]
Zheng, Lihua [2 ]
Sun, Luguo [1 ]
Song, Qiuhang [3 ]
Wang, Shuyue [1 ]
Liu, Lei [1 ]
Yu, Chunlei [2 ]
Huang, Yanxin [1 ]
机构
[1] Northeast Normal Univ, Natl Engn Lab Druggable Gene & Prot Screening, Changchun 130024, Peoples R China
[2] Northeast Normal Univ, Minist Educ, Res Ctr Agr & Med Gene Engn, Changchun 130024, Peoples R China
[3] Hebei Univ Chinese Med, Hebei Key Lab Chinese Med Res Cardiocerebrovasc D, Shijiazhuang, Hebei, Peoples R China
来源
关键词
HDACi; EOC; c-Myc; HDAC7; HISTONE DEACETYLASE INHIBITORS; SUBEROYLANILIDE HYDROXAMIC ACID; HEPATOCELLULAR-CARCINOMA; RIBOSOME BIOGENESIS; VALPROIC ACID; OPEN-LABEL; PHASE-II; S PHASE; THERAPY; CYCLE;
D O I
10.7150/ijbs.62339
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:3493 / 3507
页数:15
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