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dc.contributor.authorYa-Ling Huangen_US
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dc.description.abstract肺癌是國人十大癌症死因之首,也是造成全世界最多人死亡的癌症,肺癌致死的主因為確診時惡性腫瘤通常已轉移,能存活超過五年的患者僅有16%。目前臨床使用的標靶藥物受到不同肺癌突變型態與抗藥性的影響而使效果受到限制,因此本研究的目的在於探討具有抑癌潛力的小分子精油的相關分子機制,以及是否能抑制高轉移性肺癌細胞的轉移,作為人類非小細胞肺癌新的治療藥物。單萜烯類α-Pinene是乳香精油的主要成分,過去研究已知其具有抗菌、抗發炎與抗癌等生物活性。根據本研究的結果證明,α-Pinene可以有效抑制A549人類非小細胞肺癌細胞株的存活率,並且以TNF-α/RIP訊息傳遞路徑誘導A549細胞走向程序細細胞壞死(Necroptosis),同時產生大量Reactive oxygen species (ROS),造成A549細胞內DNA受損。低濃度的α-Pinene可以有效抑制A549細胞爬行與侵襲的能力,並影響epithelial-mesenchymal transition (EMT)相關蛋白質的表現量來抑制A549細胞的轉移。zh_TW
dc.description.abstractLung cancer is the leading cause of cancer-related deaths in the world. The 5-y survival rate for lung cancer is around 16% of diagnosed cases. Much of the lethality of lung cancer is due to frequent diagnosis of the malignancy at the metastatic stage. α-Pinene is one of the members of monoterpene and is present in frankincense essential oil. a-Pinene have been attributed biological properties, including antimicrobial , antihypertensive, antinociceptive , and anti-inflammatory. Aims of this study are trying to examine the antitumor effect of α-Pinene in A549 human non-small-cell lung cancer (NSCLC) cell. In this study, we showed that α-Pinene inhibits A549 cell viability inducing necroptosis as evidenced by MTT assay ,flow cytometric analysis and western blot . We identify α-Pinene triggers A549 necroptosis through TNF-α/RIP-dependent signaling pathway,and induces reactive oxygen species (ROS) generation that causes A549 cells DNA damage,then we test whether α-Pinene affects metastasis of A549 cells. We found that low concentration of α-Pinene can significantly inhibit migration and invasion ability in A549 cells. These findings provide an in-depth insight into the molecular mechanism of α-Pinene in the treatment of human non-small-cell lung cancer.en_US
dc.description.tableofcontents目錄 摘要 i Abstract ii 目錄 iii 圖表目次 vii 第一章、前言 1 一、癌症 1 二、肺癌 1 (一) 肺癌分類 2 (二) 肺癌成因 2 (三) 肺癌臨床治療面臨的困難 4 三、乳香精油 (Frankincense essential oil) 7 四、α-pinene之介紹與相關研究 8 五、細胞死亡方式 9 (一) 凋亡(Apoptosis) 9 (二) 壞死(Necrosis) 10 六、程序性細胞壞死(Necroptosis) 11 (一) 程序性細胞壞死之訊息傳遞路徑 11 (二)程序性細胞壞死與Reactive oxygen species (ROS)之產生 13 七、Reactive oxygen species (ROS) 14 八、Epithelial-mesenchymal transition (EMT) 14 九、研究動機 16 第二章、實驗材料與方法 17 一、實驗材料 17 (一) 實驗藥品 17 (二) 實驗抗體 19 (三) 實驗耗材 20 (四) 實驗儀器 21 (五) 實驗溶液配方 24 二、實驗原理與方法 27 (一) α-Pinene藥品置備 27 (二) 細胞培養與繼代 27 (三) 細胞冷凍與解凍 28 (四) MTT Assay細胞存活率分析 28 (五) Cell Morphology Observation細胞型態觀察 29 (六) Western Blot 西方墨點法 30 (七) Annexin V / Propidium Iodide (PI) Assay 34 (八) Reactive Oxygen Species Test 35 (九) APO-BrdU (TUNEL) DNA Fragmentation Assay 36 (十) Wound Healing Assay 細胞爬行能力測試 38 (十一) Invasion Assay 細胞侵襲能力測試 38 第三章、實驗結果 40 一、α-Pinene對肺癌細胞株存活率之影響 40 二、α-Pinene對A549非小細胞肺癌細胞型態之影響 42 三、α-Pinene誘導A549非小細胞肺癌細胞死亡方式之測定 43 四、α-Pinene誘導A549非小細胞肺癌細胞產生Reactive oxygen species (ROS)之測試 47 五、α-Pinene促使A549非小細胞肺癌細胞DNA受損之測試 49 六、α-Pinene抑制A549非小細胞肺癌細胞epithelial-mesenchymal transition (EMT)之測試 51 第四章、討論 55 第五章、參考文獻 58zh_TW
dc.subjecthuman non-small-cell lung canceren_US
dc.titleα-Pinene induces TNF-α/RIP-dependent necroptosis and inhibits metastasis in human non-small-cell lung canceren_US
dc.typethesis and dissertationen_US
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