BP023W在頭頸癌中的細胞毒性與調控機制

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姓名

楊佳馨(Chia-Hsin Yang) 查詢紙本館藏

畢業系所

系統生物與生物資訊研究所

論文名稱

BP023W在頭頸癌中的細胞毒性與調控機制
(The Cytotoxic Effects and the Regulatory Mechanism of BP023W on Head and Neck Cancer)

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摘要(中)

頭頸癌是全世界最常見的六大癌症之一，每年都有超過350,000人因頭頸癌死亡。超過75%的頭頸癌病患都是因為長期的抽菸與酗酒而導致癌症。頭頸癌患者通常都在癌症後期才被診斷，治療後的預後效果也不如預期，化療的藥物也伴隨著嚴重的副作用。中草藥治療已經在中國已經有多年的記載並且指出有較低的毒性與副作用。我們希望透過中草藥找到能夠治療頭頸癌並且不要造成病患有嚴重副作用與降低藥物毒性所造成的影響。我們首先從54種中藥中做篩選，篩選出麻黃 (BP023W) 做為候選藥物。從實驗中我們確實看見了麻黃能夠有效的抑制頭頸癌細胞株的生長。我們利用流式細胞儀檢視出BP023W對於頭頸癌細胞株不是抑制生長而是促使細胞走向死亡，並且利用西方墨點法發現BP023W在高濃度時細胞程序性凋亡蛋白被啟動，證明細胞走向凋亡。最後我們透過次世代定序更全面的探討麻黃在頭頸癌細胞株中的調控，在分析過程中確實也看到的大量與死亡相關的調控機制來證明確實麻黃是造成頭頸癌細胞凋亡。因此，我們認為BP023W可能可以成作為頭頸癌的一個治療的候選藥物。

摘要(英)

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, resulting in more than 350,000 deaths every year. More than 75% of cases of HNSCC are attributable to long-term smoking and alcohol consumption. HNSCC patients are often diagnosed at a late stage and the prognosis is poor. Chemotherapy is the mainstream treatment, but often causes serious side effects. Traditional Chinese medicines (TCMs) herbs have been documented for medical use in China for many years. Studies have found that TCMs can reduce the incidence of chemotherapy-induced side effects. In this study, we screened 54 TCMs and found that BP023W, a family of Ephedra. BP023W was found to inhibit the cell viability of Head and neck cancer (HNC) cell lines by Alarmar Blue assay. The term of apoptosis was proved by western blotting and flow cytometry in our study. The RNA sequencing data also showed that BP023 can induce HNC cell lines apoptosis. In the end, we think BP023W might be a candidate for HNC treatment.

關鍵字(中)

★ 頭頸部麟狀上皮細胞癌
★ 中草藥
★ 次世代定序
★ 生物資訊
★ 細胞凋亡

關鍵字(英)

★ Head and Neck squamous cell carcinoma
★ Traditional Chinese Medicine
★ RNA-seq
★ Bioinformatics
★ Apoptosis

論文目次

中文摘要 I
Abstract II
誌謝 III
Table of contents IV
List of Tables VI
List of Figures VII
List of Supplements Tables VIII
List of Supplements Figure IX
1.Introduction 1
2. Materials and methods 3
2-1. Cell lines and cell culture condition 3
2-2. Preparation of BP023W 3
2-3. Cell viability assay 4
2-4. Apoptosis and cell cycle assay 4
2-5. Protein preparation 4
2-6. Western blotting 5
2-7. RNA extraction 5
2-8. Data analysis 6
3. Result 7
3-1. TCMs drug screening system 7
3-2. BP023W induce cell apoptosis on HNC cell lines 10
3-2-1. BP023W cytotoxicity study by Alarmar Blue 10
3-2-2. Apoptosis and Cell cycle analysis by flow cytometry 12
3-2-3. Western blotting analyzed the expression of apoptosis-related proteins. 14
3-3. Bioinformatics analysis 16
3-3-1. RNA sequencing analysis 16
3-3-2. Functional and pathway analysis 17
4. Discussion 20
5. Reference 28
6. Supplements 31

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指導教授

蘇立仁

審核日期

2018-8-16

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