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OALib Journal期刊
ISSN: 2333-9721
费用：99美元
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蛋白质精氨酸甲基转移酶抑制剂db75对人膀胱癌t24细胞的抑制作用
DOI: 10.3724/SP.J.1145.2014.09036, PP. 57-60
Keywords: 膀胱癌,prmt1,db75,细胞凋亡
Abstract:
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，48h半数抑制浓度ic50为2.2μmol/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.
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