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 ZENG Zhongqiu,MA Yuling,PEI Zhe,et al.Inhibitory effect of protein arginine methyltransferase 1 inhibitor DB75 on bladder cancer T24 cells[J].Chinese Journal of Applied & Environmental Biology,2015,21(01):57-60.[doi:10.3724/SP.J.1145.2014.09036]





Inhibitory effect of protein arginine methyltransferase 1 inhibitor DB75 on bladder cancer T24 cells
曾中秋 马玉玲 裴哲 陈雨文 王晶 唐亚雄
中国科学院成都生物研究所 成都 610041
ZENG Zhongqiu MA Yuling PEI Zhe CHEN Yuwen WANG Jing TANG Yaxiong
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China
bladder cancer PRMT1 DB75 apoptosis
R965 : R979.1
蛋白质精氨酸甲基转移酶1(PRMT1)是近年来新发现的一种表观遗传修饰酶,在膀胱癌等多种癌组织中过度表达,因此针对该靶点的新型表观抗肿瘤药物研究尤为重要. 通过基于PRMT1药效团虚拟筛选模型筛查抑制PRMT1活性的小分子化合物,体外研究了靶向PRMT1的小分子化合物DB75对膀胱癌细胞的抗瘤活性及诱导细胞凋亡的分子机制. 实验结果显示:通过筛选体系获得了能显著抑制PRMT1活性的小分子化合物DB75;MTT实验表明,DB75能够显著(P < 0.05)地抑制膀胱癌T24细胞的增殖,且随着药物浓度的增加,抑制率呈明显的剂量效应,48 h半数抑制浓度IC50为2.2 μmol/L;DAPI染色显示DB75能显著(P < 0.05)诱导膀胱癌T24细胞凋亡;分子机制研究显示,DB75通过激活Caspase-3和PARP活性从而诱导T24细胞凋亡. 以上结果初步表明DB75可作为一种新型的膀胱癌表观先导化合物.
Protein arginine methyltransferase 1 (PRMT1), as a newly discovered epigenetic modified enzyme, is overexpressed in many cancers including bladder cancer and plays a crucial role in malignant transformation. Therefore, PRMT1 may be a novel valuable therapeutic target for cancer chemoprevention. In our study, DB75 was identified as a PRMT1 inhibitor by using the pharmacophore-based virtual screening system, and the antitumor potential and molecular mechanism of DB75 were further evaluated in vitro. The experimental results showed that DB75 signi?cantly suppressed the proliferation of bladder cancer T24 cells in a dose-dependent manner, with the IC50 value as 2.2 μmol/L after 48 h exposure to DB75. In addition, DB75 induced apoptosis in T24 cells. Altogether, DB75 could activate Caspase-3 and PARP activity, and lead to marked apoptotic effect on bladder cancer T24 cells. Together, these ?ndings suggested that DB75 may be a promising epigenetic lead compound for prevention and treatment of bladder cancer.


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四川省国际合作计划(2013HH0014)和国家自然科学基金项目(81173095)资助 Supported by the International Cooperation Program of Sichuan, China (2013HH0014) and the National Natural Science Foundation of China (81173095)
更新日期/Last Update: 2015-02-15