合成之多甲氧基黃酮類化合物對胰臟癌腫瘤生成的抑制效果

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Title:	合成之多甲氧基黃酮類化合物對胰臟癌腫瘤生成的抑制效果 The inhibitory effect of polymethoxyflavone derivatives on pancreatic tumorigenesis
Authors:	王建鈞
Contributors:	生物科技系田孝威汪文忠
Keywords:	黃酮胰臟癌細胞纖維母細胞共同培養 flavones pancreatic cancer cells fibroblasts co-culture
Date:	2017
Issue Date:	2018-01-11 11:45:09 (UTC+8)
Abstract:	一些從柑橘類水果純化出來的多甲氧基黃酮類化合物，例如sinensetin (5,6,7,3',4'-pentamethoxyflavone)，被研究具有抗癌活性，且其毒性不高。本篇研究以3,4,5-trimethoxyphenol為起始物合成了一個sinensetin的結構類似物4'-hydroxy-5,6,7,3'-tetramethoxyflavone，並以洋菜膠細胞群落形成試驗測試此化合物與其前驅物等之抗腫瘤生成活性，結果顯示除了3,4,5-trimethoxyphenol 與1-(6-Hydroxy-2,3,4-trimethoxy-phenyl)-ethanone對胰臟癌細胞PANC-1之腫瘤生成無顯著抑制效果外，其餘數種化合物皆可抑制胰臟癌細胞之腫瘤形成。如果同時以胰臟癌纖維母細胞PC-015Ct共同培養進行胰臟癌細胞PANC-1之洋菜膠細胞群落形成試驗，則會顯著地減低抗癌藥物gemcitabine的抑制腫瘤生成效果，顯示纖維母細胞可增進癌細胞之抗藥性。以此檢視本研究使用或合成出來的化合物之抗腫瘤生成活性，發現這些化合物的抑癌活性並不受纖維母細胞PC-015Ct共同培養的影響。本篇研究顯示數種新合成之多甲氧基黃酮類化合物具有抑制胰臟癌腫瘤生成的活性，然其作用機制尚待進一步研究探討。 Some polymethoxylated flavones, such as sinensetin (5,6,7,3',4'-pentamethoxyflavone), isolated from citrus, have been shown to possess anti-cancer activity and lower toxicity. We synthesized 4'-hydroxy-5,6,7,3'-tetramethoxyflavone, a sinensetin analog, from 3,4,5-trimethoxyphenol. The anti-tumorigenesis activity of compounds used and produced in the process of synthesis reactions was tested by soft agar colony formation assay. The results showed that all the compounds, but not 3,4,5-trimethoxyphenol and 1-(6-Hydroxy-2,3,4-trimethoxy-phenyl)-ethanone, had inhibitory effects on colony formation of pancreatic cancer PANC-1 cells. The anti-tumorigenesis activity of gemcitabine was significantly decreased by fibroblasts, which was revealed by colony formation assay of pancreatic cancer PANC-1 cells with co-culture of pancreatic cancer-associated fibroblast PC-015Ct. The results showed the drug resistance occurred when pancreatic cancer cells grew with surrounding fibroblasts. However, the anti-tumorigenesis activity of tested compounds was not influenced with co-culture of PC-015Ct fibroblasts. In this study, we showed some novel polymethoxyflavone derivatives possess anti-tumorigenesis activity towards pancreatic cancer. The inhibitory mechanism of these compounds will be still elucidated.
Relation:	電子全文公開日期：2020-01-31，學年度：105，65頁
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Dissertations and Theses

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