HAC-Y6 及CHM-1之抗癌活性評估
主題一、新穎微管聚合抑制劑HAC-Y6藉由活化死亡接受體4訊息路徑造成肝癌細胞凋亡
主題二、利用蛋白質體學方式探討非小細胞肺癌對doxorubicin 抗藥性的機制

CMUR > College of Life Sciences > Department of Biological Science and Technology > Theses & dissertations > Item 310903500/32482

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Title:	HAC-Y6 及CHM-1之抗癌活性評估主題一、新穎微管聚合抑制劑HAC-Y6藉由活化死亡接受體4訊息路徑造成肝癌細胞凋亡主題二、利用蛋白質體學方式探討非小細胞肺癌對doxorubicin 抗藥性的機制 Anti-cancer activity evaluation of HAC-Y6 and CHM-1 Patr 1. Induction of apoptosis by HAC-Y6, a novel synthetic microtubule inhibitor, in human hepatocellular carcinoma cells through activation of death receptor 4 signaling pathway Part2. Proteomic analysis of doxorubicin-resistance mechanisms in non-small cell lung cancer cell line
Authors:	白詩婷;Shih-Ting Bai
Contributors:	生命科學院生物科技學系碩士班
Keywords:	HAC-Y6；肝癌；微管；死亡接受體4； p38;HAC-Y6； Hepatocellular carcinoma cells； Microtubule inhibitor； Death receptor 4； p38
Date:	2010
Issue Date:	2010-09-29 12:06:47 (UTC+8)
Abstract:	干擾及抑制微管功能的化合物，已經廣泛成為治療癌症的藥物。?剷?類生物鹼的類似物被證明具有許多生物活性，包括:抗氧化、抗微生物、抗瘧疾、抗病毒及抗癌。本研究主要證明?剷?類生物鹼衍生物在抗癌中的機制。本研究顯示，6-acetyl-9-(3,4,5-trimethoxybenzyl)-9H-pyrido[2,3-b]indole(HAC-Y6)，一種新穎的化合物，具有抗人類肝癌活性的效果。在本研究中，西方墨點法及免疫螢光染色實驗中發現，HAC-Y6具有相似於秋水仙素的功效，能夠抑制微管的聚合。流式細胞儀分析中可發現，利用HAC-Y6處理Hep3B細胞，會使細胞週期停滯在G2/M週期並且造成細胞凋亡。因此，HAC-Y6會影響Hep3B細胞的細胞週期及細胞凋亡的相關蛋白質表現。此外，在西方墨點法實驗中，HAC-Y6能誘導caspase-3, 8, 9、Bax和 Bcl-2 family的表現，並且，HAC-Y6也能活化Bid，caspase-8的表現。在外在路徑中，HAC-Y6能活化DR4的表現。然而，HAC-Y6也能使p38磷酸化上升。綜合以上實驗結果發現，HAC-Y6能夠藉由抑制Hep3B細胞微管的聚合，使的細胞週期滯留在G2/M週期，並且能藉由外在路徑及內在路徑去誘導細胞凋亡而抑制腫瘤的生長。因此本研究可以證明，新穎化合物，HAC-Y6有希望能夠成為一個微管抑制劑，在肝癌的治療上具有很大的潛能。 The present data showed that a novel synthesized compound, 6-acetyl-9-(3,4,5-trimethoxybenzyl)-9H-pyrido[2,3-b]indole (HAC-Y6), exhibited potent antitumor activity against human hepatocellular carcinoma (HCC) cells in vitro. Western blot and immunofluorescence experiments indicated that HAC-Y6 depolymerized microtubules similar to the effect of colchicine. HAC-Y6-treatment in Hep3B cells resulted in the accumulation of G2/M phase and finally induced apoptosis assessed by flow cytometry analysis. In addition, HAC-Y6-treatment influenced the expression of cell cycle and apoptosis related proteins in Hep3B cells. Western blot experiments indicated that HAC-Y6 exposure augmented caspase 3, 8, 9 and Bax protein levels, while attenuating the expression of Bcl-2 family proteins. Moreover, Bid, a substrate of caspase-8, was also activated by HAC-Y6. Treatment of HAC-Y6 caused the upregulation of death receptor 4 (DR4). Interestingly, HAC-Y6 treatment promoted phosphorylation of p38. Taken together, all the data demonstrated hat HAC-Y6 exhibited its antitumor activity through disrupting the microtubule assembly, causing cell cycle arrest and induce apoptosis through both extrinsic and intrinsic pathways in Hep3B cells. Therefore, the novel compound HAC-Y6 is a promising microtubule inhibitor that has great potentials for therapeutic treatment of HCC. Key words: HAC-Y6, Hepatocellular carcinoma cells, Microtubule inhibitor, Death receptor 4, p38
Appears in Collections:	[Department of Biological Science and Technology] Theses & dissertations

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