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系統識別號 U0026-0812200913503848
論文名稱(中文) 缺氧對前列腺素合成酵素-2表現量的調控
論文名稱(英文) The effect of hypoxia on potentiation of cyclooxygenase-2 expression
校院名稱 成功大學
系所名稱(中) 生理學研究所
系所名稱(英) Department of Physiology
學年度 95
學期 2
出版年 96
研究生(中文) 古士宜
研究生(英文) Shi-Yi Kuu
學號 s3694403
學位類別 碩士
語文別 中文
論文頁數 44頁
口試委員 口試委員-吳孟興
口試委員-林永明
指導教授-蔡少正
中文關鍵字 缺氧  前列腺素合成酵素-2 
英文關鍵字 cyclooxygenase-2  hypoxia 
學科別分類
中文摘要 前列腺素G/H合成脢-2在許多病理組織中,如癌症及子宮內膜異位細胞中都會過度表現,並且伴隨著疾病的惡性化嚴重性增加及較差的癒後狀況。但這些組織中產生過度表現前列腺素G/H合成脢-2的機制卻還不清楚。我們是首次以子宮內膜異位症為模式,假設在異位基質細胞中過度表現的前列腺素G/H合成脢-2是因為缺氧修飾造成其對於細胞介素刺激的敏感度升高。要證實這項假設,我們讓原位的子宮內膜基質細胞經歷缺氧後看前列腺素G/H合成脢-2的反應表現。缺氧對於前列腺素G/H合成脢-2的敏感度的影響,因子宮內膜細胞來源不同而有個體差異,其中半數的個案都顯示敏感度被降低。而缺氧預處理在子宮頸癌細胞株對於介白素-1刍的刺激,是會增加前列腺素G/H合成脢-2啟動子活性但降低蛋白表現量。但是在子宮內膜癌細胞株中,不論單純缺氧或缺氧預處理,都可以增加前列腺素G/H合成脢-2的表現量。這樣的結果暗示缺氧對於前列腺素G/H合成脢-2在不同細胞中的表現有截然不同的影響。進一步探討缺氧造成不同前列腺素G/H合成脢-2敏感度的機制將有助於暸解此現象對於癌症細胞的生物重要性。
英文摘要 Cyclooxygenase-2 (COX-2) is overexpressed in many pathological tissues such as cancerous and endometriotic cells, which often results in increased malignancy and poor prognosis. However, mechanisms responsible for overexpression of COX-2 in these tissues are largely unkown. Here we first took endometriosis as our model and hypothesized that overexpression of COX-2 in ectopic stromal cells is likely due to hypoxia-mediated modification of COX-2 gene leading to increased sensitivity to exogenous stimuli such as proinflammatory cytokines. To test this hypothesis, we cultured eutopic endometrial stromal cells under hypoxia and examined the responsiveness of COX-2. Hypoxia had different effects on COX-2 responsiveness among patients with half of the cases tested showing down-regulation. Hypoxia pretreatment in cervical cancer cell line (HeLa cells) enhanced COX-2 promoter activity but decreased the protein expression in response to IL-1刍. However, endometrial cancer cell line treated and pretreated with hypoxia increased COX-2 expression. These results indicated that hypoxia pretreatment had different effects on COX-2 responsiveness in different tissues. The mechanisms of differential regulation of hypoxia on COX-2 should be further investigated to reveal the biological significance.
論文目次 中文摘要 …………………………………………………………………. 1
Abstract …………………………………………………………………. 2
緒論 …………………………………………………………………. 3
材料與方法 …………………………………………………………………. 11
子宮內膜異位症病人檢體之收集與培養……………………. 11
缺氧處理..................................................................................... 11
萃取細胞蛋白質………………………………………………. 11
蛋白濃度分析(Lowry assay)………………………………. 12
西方轉漬法(Western blot)…………………………………. 12
製備小量質體DNA (Minipreparation of plasmid DNA)……... 13
細胞轉殖……………………………………………………….. 14
螢光酵素及Beta-半乳糖苷酶檢測…………………………… 15
統計分析………………………………………………………. 15
結果 …………………………………………………………………. 16
前列腺素G/H合成脢-2對於缺氧及介白素-1刍刺激在子宮內膜基質細胞依病人有不同的反應…………………………. 16
缺氧預處理的子宮頸癌細胞株會增加介白素-1刍刺激的前列腺素G/H合成脢-2啟動子活性,但降低其蛋白表現量…… 16
單純缺氧處理和缺氧預處理在子宮內膜癌細胞株中都會增加前列腺素G/H合成脢-2 的表現量……………………….. 17
討論 …………………………………………………………………. 24
附錄 …………………………………………………………………. 28
子宮內膜細胞來源的病人臨床資料及分期…………………. 28
溶液與藥品的配製……………………………………………. 29
使用藥品廠牌一覽表…………………………………………. 35
參考文獻 …………………………………………………………………. 37
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