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OALib Journal期刊
ISSN: 2333-9721
费用：99美元
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定靶突变温敏酵母模型在pin1抑制剂筛选中的应用
, PP. 854-860
Keywords: pin1,抗肿瘤,周期阻滞,细胞凋亡,裸鼠
Abstract:
利用定靶突变温敏酵母模型寻找pin1的新型抑制剂，并探讨阳性化合物的体内外抗肿瘤活性。采用mtt法、流式细胞仪法、免疫印迹法、划痕实验和虚拟对接检测阳性化合物的体外活性。利用移植瘤裸鼠模型检测阳性化合物的体内活性。结果发现，酵母模型初筛得到的阳性化合物8-11在体外，对pin1的ic50值为（10.40±1.68）μmol·l-1，能抑制多种肿瘤细胞的增殖，诱导hela细胞g1期阻滞和凋亡，降低cyclind1的蛋白水平表达，降低肿瘤细胞迁移能力，虚拟对接中与pin1的活性结构域呈现出较高的亲和性；在体内，8-11抑制裸鼠移植瘤生长。本研究首次证实8-11可通过抑制pin1发挥抗肿瘤作用。
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