文档介绍：缩略语索弓
KAT5 Lysine acetyltransferase 5 赖氨酸乙酰转移酶5 TGF—D Transforming growth factorl3 转化生长因子p VEGF Vascular endothelial growth factor 血管内皮生长因子 HMGA2 High-mobility group AT-hook2 高迁移率族蛋白A2
TSS Transcription start site 转录起始位点
HArs Histone acetyltransferase 组蛋白乙酰转移酶 DAPI 4,6·-diamiding·-2·-phenylindole 4, HRP Horseradish peroxidase 辣根过氧化物酶
Akt Protein kinase B 蛋白激酶B
II
万方数据
摘要
摘要
肺癌是严重威胁人类健康的疾病,治疗后转移复发是影响药物疗效的主要问题。JQl 和IBET-726是BET家族蛋白的选择性抑制剂,对多种肿瘤具有较理想的治疗效果。实验室前期研究结果显示,ATM信号通路及其调节的MMP一13/MMP一3表达与肺癌细胞迁移密切相关。为研究BET抑制对肺癌细胞迁移的作用及对ATM信号通路的调节机制, 我们首先通过划痕实验和Transwell实验检测BET抑制剂对肺癌细胞迁移能力的影响, 并用Western ;其次,通过使用
ATM相关通路抑制剂,探究ATM信号通路在BET抑制剂影响肺癌细胞迁移中的作用;
然后,通过Western blotting及免疫荧光检测BET抑制剂对ATM通路相关分子激活情况;最后通过过表达或敲除Brd4L,深入探究BET抑制剂通过抑制Brd4促进肺癌细胞迁移机制。我们的研究结果包括:(1)低浓度的BET抑制剂通过上调ECM降解相关蛋白酶MMP一3/;(2);(3)BET家族蛋白Brd4L可以通过抑制ATM信号通路减少肺癌细胞迁移,提示 BET抑制剂可能通过抑制Brd4L促进细胞迁移。研究结论:、低浓度促进肺癌细胞迁移,着重研究了BET抑制剂促进肺癌细胞迁移的机制,阐明了ATM信号通路在BET抑制剂诱导迁移中的重要作用,为临床上合理使用BET抑制剂提供相关理论依据。
关键词:BET抑制剂;ATM:肺癌细胞迁移;MMP一3;MMP一13
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万方数据
Abstract
Abstract
Lung cancer is one of the leading causes of human metastasis after therapy remains and IBET-726 are selective inhibitors of BET Bromodomain proteins and have potential anti—tunlor and ATM—mediated up—regulation of MMP一3/MMP-1 3 expression are closely involved in promoting lung cancer explore the effects of BET inhibitors on lung cancers migration and ATM regulation,We
firstly evaluated effect of BET inhitors on the lung cancer cell migration ability by henotic
wound scratch assay and Transwell migration ,migration associated extracellular matrix(ECM)degration marker(MMP··3/MMP··1 3)were assessed via Western related inhibitors were used to investigate its roles in BET inhibitor-induced cell migration and MMP-3/MMP一1 3 activation of ATM signal pathway up