2011-01-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/643603摘要：HDAC抑製劑是極有潛力的抗癌藥物，能誘使細胞週期停滯和細胞凋亡。然而，HDAC抑制劑對癌症進程之影響，如血管新生和癌症轉移，依然有許多未知之處。我們於各種 HDAC抑製劑中， 發現僅TSA和SAHA能誘發非小細胞肺癌細胞A549表現血管新生抑制分子 ADAMTS1 ; HDAC6專一抑製劑以及HDAC6 knockdown皆能誘發A549細胞表現ADAMTS1。藉由ADAMTS1 promoter -luciferase，發現HDAC抑制劑需要透過promoter近端之GC box方能誘發ADAMTS1表現。GC box為轉錄因子SP1之結合位，因此利用Chromatin免疫沈澱與DAPA等實驗技術，發現TSA能降低SP1與HDAC6與ADAMTS1 promoter之結合，並且吸引CBP結合至ADAMTS1 promoter上。我們的結果顯示，HDAC抑制劑誘發血管新生抑制分子ADAMTS1的過程中，HDAC6以及SP1扮演關鍵性角色。<br> Abstract: HDAC inhibitors are promising anticancer agents by inducing cell cycle arrest and apoptosis. However, the role of HDAC in cancer progression, such as angiogenesis and metastasis, remains largely unexplored. Among various HDAC inhibitors, we demonstrated that TSA and SAHA upregulated the angiostatic ADAMTS1 expression in A549 cells. HDAC6 inhibitor tubacin and HDAC6 knockdown also lead to ADAMTS1 upregulation. By reporter, DAPA and ChIP assay, we showed that the proximal GC boxes are essential for ADAMTS1 induction and decreased binding of SP1 and HDAC6 to the ADAMTS1 promoter after TSA treatment was also seen. Our data suggest the involvement of HDAC6 and SP1 in the HDACi-induced expression of angiostatic ADAMTS1.HDAC抑制劑非小細胞肺癌血管新生