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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林仁混 | |
| dc.contributor.author | Chin-Chih Liu | en |
| dc.contributor.author | 劉晉志 | zh_TW |
| dc.date.accessioned | 2021-06-15T00:15:27Z | - |
| dc.date.available | 2012-09-15 | |
| dc.date.copyright | 2009-09-15 | |
| dc.date.issued | 2009 | |
| dc.date.submitted | 2009-06-16 | |
| dc.identifier.citation | 1. Jemal A, S.R., Ward E, Hao Y, Xu J, Murray T, Thun MJ, Cancer statistics, 2008. CA Cancer J Clin, 2008. 58(2): p. 71-96.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/41299 | - |
| dc.description.abstract | 在包括攝護腺癌、乳癌、肺癌以及許多其他腫瘤組織裡發現，p27Kip1蛋白的缺乏，以及藉由參與多泛素化修飾（polyubiquitilation）來造成p27Kip1蛋白量下降的第二型S週期激酶相關蛋白（S phase kinase-associated protein 2，skp2）的過量表現，與腫瘤的惡化程度呈現高度的關係。
為了找出對於非雄性素依賴型（androgen-independent）攝護腺癌具有治療或化學預防潛能的藥物，我們篩選了多酚類物質，發現quercetin以及EGCG對非雄性素依賴型攝護腺癌細胞PC3以及DU145具有降低第二型S週期激酶相關蛋白（skp2）之mRNA與蛋白量以及抑制生長的作用。此外，quercetin會提升p27Kip1的與p21Cip1的蛋白量，EGCG則會增加p21Cip1並使p27Kip1減少。透過流式細胞儀觀察，發現在經過24小時的加藥處理後， quercetin會提升PC3細胞中的G1週期比例，EGCG則會增加sub-G1週期的比例。先前有研究指出在非雄性素依賴型攝護腺癌細胞PC3以及DU145中，阻斷PI3K-Akt訊息傳遞路徑會造成第二型S週期激酶相關蛋白（skp2）量的降低，並伴隨著p27Kip1蛋白量的增高，在本篇研究中也發現quercetin跟PI3K的專一性抑制劑LY294002都會降低Akt的磷酸化以及第二型S週期激酶相關蛋白（skp2）的mRNA以及蛋白量，並伴隨著p27Kip1蛋白量的提升。然而EGCG的處理並無法降低Akt的磷酸化。總結以上結果我們發現，quercetin透過阻斷PI3K-Akt訊息傳遞路徑以及降低第二型S週期激酶相關蛋白（skp2）的mRNA與蛋白表現量而造成p27Kip1與p21Cip1蛋白的累積，使細胞被拘留在G1週期，EGCG則會同時降低細胞第二型S週期激酶相關蛋白（skp2）以及p27Kip1的量並造成細胞凋亡（apoptosis）。 從以上的實驗結果我們發現了quercetin和EGCG透過降低第二型S週期激酶相關蛋白（skp2）表現達到抑制非雄性素依賴型攝護腺癌細胞生長的新分子機制，也顯示第二型S週期激酶相關蛋白（skp2）可能是治療攝護腺癌重要的分子標的。 | zh_TW |
| dc.description.abstract | Loss of p27Kip1 and overexpression of S phase kinase-associated protein 2 (skp2), an ubiquitin ligase subunit targets p27Kip1 for degradation by polyubiquitynation, are correlated with tumor progression in many cancers, such as prostate cancer, breast cancer, and lung cancer.
In order to find potential drugs for therapy or chemoprevention toward androgen-independent prostate cancer, we screened polyphenolic compounds and found that quercetin and EGCG both inhibited the cell growth and downregulated the mRNA and protein levels of skp2 in the human androgen-independent prostate carcinoma PC3 and DU145 cells. Furthermore, quercetin upregulated the protein levels of p27Kip1 and p21Cip1. EGCG upregulated p21Cip1 but reduced p27Kip1 level. Analyzed by flow cytometry, we found that quercetin elevated the G1 phase distribution and EGCG raised the sub-G1 phase distribution at 24 hour of treatment. The previous study has shown that blocking of PI3k-Akt pathway leads to the reduction of skp2 protein and the concomitant elevation of the p27Kip1 protein level. We also found that both quercetin and a specific PI3K inhibitor – LY294002 reduced phosphorylated Akt (pAkt) and both skp2 mRNA and protein levels. Concomitantly, protein levels of p27Kip1 and p21Cip1 are upregulated by quercetin and LY294002. However, EGCG treatment can’t reduce the phosphorylation level of Akt. Taken together, these results indicated that by blocking PI3K-Akt pathway, quercetin reduces the mRNA and protein levels of skp2 and results in accumulations of protein p27Kip1 and p21Cip1. Thus quercetin arrests cells in G1 phase. EGCG decreased both skp2 and p27Kip1 level and leads to cell apoptosis. In this study, we found that quercetin and EGCG inhibit the growth of androgen-independent prostate cancer cells via downregulating skp2 protein, a novel pharmaceutical effect of them toward prostate cancer cells. It also revealed that skp2 may be an important therapeutic molecular target against prostate cancers. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T00:15:27Z (GMT). No. of bitstreams: 1 ntu-98-R96442004-1.pdf: 2130944 bytes, checksum: d5566bf8ef86f1b1d3cec8c5f8d173db (MD5) Previous issue date: 2009 | en |
| dc.description.tableofcontents | 中文摘要:1
Abstract:2 Abbreviations:4 Introduction:5 Materials and Methods:14 Results:19 Discussion:26 References:31 Figures:47 Appendices:62 | |
| dc.language.iso | en | |
| dc.subject | 植物多酚 | zh_TW |
| dc.subject | 第二型S週期激酶 | zh_TW |
| dc.subject | 相關蛋白 | zh_TW |
| dc.subject | 攝護腺癌 | zh_TW |
| dc.subject | 槲皮素 | zh_TW |
| dc.subject | 表沒食子兒茶素沒食子酸酯 | zh_TW |
| dc.subject | p21 | en |
| dc.subject | PC3 | en |
| dc.subject | EGCG | en |
| dc.subject | skp2 | en |
| dc.subject | p27 | en |
| dc.subject | quercetin | en |
| dc.title | Quercetin與EGCG抑制攝護腺腫瘤細胞生長機制之探討 | zh_TW |
| dc.title | Quercetin and EGCG inhibit the growth of human prostate carcinoma cells by down-regulation of skp2 protein | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 97-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 蕭水銀,周綠蘋,何元順,陳彥州 | |
| dc.subject.keyword | 第二型S週期激酶,相關蛋白,攝護腺癌,槲皮素,表沒食子兒茶素沒食子酸酯,植物多酚, | zh_TW |
| dc.subject.keyword | skp2,p27,p21,quercetin,EGCG,PC3, | en |
| dc.relation.page | 69 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2009-06-17 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
| 顯示於系所單位： | 生物化學暨分子生物學科研究所 | |
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| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-98-1.pdf 未授權公開取用 | 2.08 MB | Adobe PDF |
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