Tyloxapol 在大腸癌細胞中的特異性及作用機制之研究

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姓名

江昀儒(Yun-ru Chiang) 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

Tyloxapol 在大腸癌細胞中的特異性及作用機制之研究
(The specificity and mechanisms of tyloxapol in colorectal cancer cells)

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摘要(中)

癌症現在為全球需要面對的議題, 在目前的藥物治療中，化療藥物伴隨著負作用，並且，標靶藥物治療只適用於少部分的癌症病患。經過一連串癌細胞存活率測試，我們發現Tyloxapol具有抑制癌細胞增生的能力，它目前是一種清除支氣管和肺部黏液的用藥。此研究證明Tyloxapol具有潛力成為標靶藥物，未來我們希望能有一些活體研究的證明，將Tyloxapol確實發展成為抗癌藥物的可能性。

摘要(英)

Cancer is a lethal cause of morbidity and mortality worldwide. In current therapies, patients suffer from side effects in chemotherapy, and targeted therapy could only be suitable for some of cancer patients. In our study, we explored the possibility of tyloxapol becoming a repurposing drug in cancer therapy. Our results present here should be analyzed in vivo in the future. Hopefully, tyloxapol can be potentially useful as a new targeted therapy drug in CRC treatment.

關鍵字(中)

★ 泰洛沙泊
★ 大腸癌
★ 訊息傳遞路徑

關鍵字(英)

★ Tyloxapol
★ Colorectal carcinoma
★ PI3K
★ MAPK

論文目次

Abstract in Chinese ....................................i
Abstract in English ...................................ii
Abbreviations ........................................iii
Acknowledgements ......................................iv
Table of contents ......................................v
Figure legends ...................................vii
Ⅰ. Introduction ........................................1
1. Human colorectal carcinoma ......................1
2. CRC related gene mutations and pathways .............2
3. Targeted cancer therapy .............................3
4. Repurposing drugs ...................................4
5. Tyloxapol ...........................................5
6. The purposes of this study ..........................6
Ⅱ. Materials and methods ...............................7
1. Materials ...........................................7
1.1 Cell lines .........................................7
1.2 Reagents ...........................................8
1.3 Plasmids ...........................................8
1.4 Antibodies .........................................8
2. Methods .............................................8
2.1 Cell survival assay ................................8
2.2 Cell transfection ..................................9
2.3 Preparation of protein extracts ....................9
2.4 Western blot analysis .............................10
2.5 DNA fragmentation assay ...........................10
2.4 Colony formation assay ............................11
Ⅲ. Results
1. Tyloxapol inhibits cell survival with different sensitivities in different genetic backgrounds of colon cancer cell lines ....................................12
2. Tyloxapol reduces cell cycle progression and induces apoptosis .............................................13
3. Tyloxapol represses tumorigenesis ..................14
4. The survival rate of PI3K wild type cells in response to tyloxapol increase after AKT activation ...............14
5. p53 has no effects on cell survival in response to tyloxapol treatment ...................................15
6. The synergetic effect of PI3K inhibitor with tyloxapol enhanced the growth inhibitory in PI3K mutation cells 15
Ⅳ. Discussion and future aspect ..................... .16
1. The mechanisms of tyloxapol repress cancer cell growth
2. The effects of tyloxapol influence cell signaling transduction pathways .................................16
3. The effects of combination treatment enhance cell death in PI3K mutation cells ............................17
4. Future works .......................................18
Ⅴ. References .....................................19
Figures ..............................................22

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指導教授

馬念涵(Nianhan Ma)

審核日期

2013-6-27

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