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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 潘思樺(Szu-Hua Pan) | |
| dc.contributor.author | Tan-Ching Wang | en |
| dc.contributor.author | 王丹青 | zh_TW |
| dc.date.accessioned | 2023-03-19T21:07:26Z | - |
| dc.date.copyright | 2022-10-04 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-09-17 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/83431 | - |
| dc.description.abstract | 肺癌在全球癌症死亡人數比例中一直是名列前茅的佼佼者，除了因其不易被早期診斷外，另一項主要的原因就是患者有極高的機率在病程早期發生癌轉移的情況。目前，肺癌的治療仍存在許多的侷限性，轉移與藥物的抗藥性的產生是臨床常見的棘手問題，隨著病況的改變，病人往往需要接受更高強度的治療，伴隨而來的便是虛弱與副作用的發生；此時，許多的病人常會自行尋求營養補充像是亞麻籽油等以作為輔助治療，期望可以藉此延緩癌症進程。亞麻籽油富含大量α-次亞麻油酸(ALA)，其對於人類屬於一種必須脂肪酸，人體無法自行合成，須透過食物加以攝取，多數會儲存於身體組織中，進而在體內發揮潛在生理功能。目前，對於ALA是否能有效抑制肺癌細胞的轉移及其相關的調控機轉並不十分清楚；因此，在本研究中我們嘗試釐清ALA對於癌細胞侵襲與轉移能力之調控影響。首先，我們藉由細胞存活實驗找出不影響癌細胞增生之ALA添加劑量。後續，利用體外細胞培養的研究結果發現，ALA可促使高侵襲力肺癌細胞(CL1-2、CL1-5、Hop62和A549)產生類間質細胞上皮轉化 (MET-like)、抑制癌細胞的移動和侵襲、促進細胞骨架重排並使細胞整體的厚度增加。此外，我們利用全蛋白質體分析技術進一步找出可能參與ALA影響細胞轉移作用有關的作用蛋白並加以驗證。最後，更透過動物實驗以再次驗證ALA在動物體抑制肺癌轉移的能力。綜合上述結果，我們認為ALA在臨床上或許能作為一種有效的天然預防物，以協助延緩肺癌病患病情的惡化。 | zh_TW |
| dc.description.abstract | Lung cancer is the leading cause of cancer mortality worldwide. In addition to the delayed diagnosis, early metastasis and drug resistance are big challenges for lung cancer treatment, which not only accelerate cancer progression but also make patients more debilitated. Thus, many people tend to seek nutritional supports such as flaxseed oil to relieve their symptoms and hope to prolong their life. Flaxseed oil contains 50 to 60% alpha-linolenic acid (ALA), which is an essential fatty acid, stored in tissue pools, and benefits per se against cancer owing to its good bioavailability. Till now, the exact molecular mechanism of how ALA ameliorates cancer metastasis is still unclear. Thus, we tried to explore whether ALA treatment could affect the malignant behavior of highly invasive lung cancer cells. First, we determined the treatment concentration of ALA according to the IC50 of these cells. Then, we displayed that ALA treatments led cells to process mesenchymal-epithelial transition (MET), suppress their migratory and invasive abilities, promote cytoskeletal rearrangement, and increase cell thickness in vitro. Further, we identified potential candidates involved in ALA-mediated regulation of cancer metastasis through proteomic analysis. In the end, we demonstrated that ALA could inhibit lung cancer metastasis in vivo. All the results enlightened the role of ALA in inhibiting lung cancer metastasis. | en |
| dc.description.provenance | Made available in DSpace on 2023-03-19T21:07:26Z (GMT). No. of bitstreams: 1 U0001-1009202216190300.pdf: 14767979 bytes, checksum: 80d6fc84657ad64b13bbd7dd52cd3c3e (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | 致謝 ? 中文摘要 ? Abstract ? Contents iv List of Figures x List of Tables xiii List of Appendices xiv Chapter One: Introduction 1 1.1 Lung cancer 1 1.1.1 The epidemiology of NSCLC 1 1.1.2 The risk factors for lung cancer 2 1.1.3 The histological classification of lung cancer 3 1.1.4 Stages of NSCLC 5 1.1.5 Treatments for NSCLC 8 1.1.6 Challenge in NSCLC therapy 10 1.2 Processing steps of thickness measurement 12 1.2.1 Cell migration and invasion involved in cancer metastatic process 12 1.2.2 Epithelial-to-mesenchymal transition (EMT) 13 1.2.3 Cytoskeletal rearrangement 15 1.3. Potential supportive medicine for lung cancer 16 1.3.1 Nutrition: Oil supplements 161.3.2 The importance of evidence-based research on nutrition and cancer 17 1.3.3 The difference between omega-3, 6, and 9 fatty acids 18 1.3.4 The benefits of omega-3 fatty acids for lung cancer patients 21 1.3.5 Flaxseed oil is rich in α-linolenic acid (ALA) 23 1.3.6 Alpha-linolenic acid (ALA) 24 1.3.7 The metabolism of ALA in humans 25 1.3.8 The proven benefits of ALA 28 1.4 Research background and motives 30 Chapter Two: Materials 32 2.1 Cell line 32 2.2 Animal 32 2.3 Instrument and device 32 2.4 Antibody 33 2.5 Kit 34 2.6 Pharmaceutical 35 2.7 Analysis software 37 Chapter Three: Methods 38 3.1 Cell lines and culture conditions 38 3.2 Preparation of ALA solution 38 3.3 Sulforhodamine B (SRB) assay 39 3.4 Doubling time assay 40 3.5 Oil Red O staining 41 3.6 Microscopy examination 42 3.7 Immunoblotting 42 3.8 2-well wound healing assay 43 3.9 Modified Boyden chamber invasion assay 44 3.10 F-actin staining 45 3.11 Experimental metastasis in vivo 47 3.12 Total proteome analysis 48 3.13 Quantitative phase bio-imaging for thickness 52 3.14 Statistical analysis 53 Chapter Four: Results 54 4.1 Aim one: ALA supplements can affect metastasis-related cellular functions of lung cancer cells 54 4.1.1 The appropriate ALA concentration for the highly invasive CL1-5 cell line was measured 54 4.1.2 Treatment of ALA for 24 hours makes highly invasive CL1-5 cells ingest a certain amount of ALA and change their morphology 55 4.1.3 ALA supplements induce MET in highly invasive lung cancer cell lines 56 4.1.4 ALA suppresses the migratory abilities of highly invasive lung cancer cell lines in a dose-dependent manner 58 4.1.5 ALA reduces the invasive abilities of highly invasive lung cancer cell lines in a dose-dependent manner 59 4.1.6 ALA significantly promotes cytoskeletal rearrangement of highly invasive lung cancer cell lines 59 4.1.7 ALA suppresses lung cancer metastasis in vivo 60 4.2 Aim two: The molecular mechanism of how ALA ameliorates lung cancer metastasis is explored 62 4.2.1 Total proteome analysis was applied to find potential candidates involved in the signal pathways 62 4.2.2 The selected top-regulated candidates are validated by immunoblotting and their survival analysis for patients with lung cancer 64 4.2.3 DDRGK, ZN701, and THBG are possible top 3 proteins involved in signal pathways that ALA regulates for ameliorating lung cancer metastasis 65 Chapter Five: Discussion 87 5.1 There are similarities and differences in characteristics among cell lines we used 87 5.2 It may be practicable to reach 100-150 μM ALA in human plasma by intake of ALA supplements 88 5.3 The ALA concentration of commercial flaxseed supplements is compared with the effective ALA dose in this study 91 5.4 Several foods are high in ALA 91 5.5 More improved directions in animal experiments can be implemented in the future 92 5.6 It is required to conduct recused experiments for the 3 selected candidates from ranking 94 5.7 The clear mechanism from total proteome analysis may be improved in several ways 94 5.8 ALA may alter membrane rigidity and then influence intracellular signaling 97 5.9 ALA supplements make CL1-5 cells thicker 98 5.10 Membrane rigidity may be related to cancer metastasis 100 5.11 Membrane proteome analysis should be undertaken in the future 100 Chapter Six: Conclusion 102 Abbreviation 104 References 106 Appendix 115 | |
| dc.language.iso | en | |
| dc.title | 次亞麻油酸在抑制肺癌轉移之角色探討及研究 | zh_TW |
| dc.title | The role of α-Linolenic Acid in Inhibition of Lung Cancer Metastasis | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 110-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 邱琬淳(Wan-Chun Chiu),張以承(Yi-Cheng Chang) | |
| dc.subject.keyword | α-次亞麻油酸,轉移,肺癌,亞麻籽油, | zh_TW |
| dc.subject.keyword | Alpha-linolenic acid,metastasis,lung cancer,flaxseed oil, | en |
| dc.relation.page | 157 | |
| dc.identifier.doi | 10.6342/NTU202203272 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2022-09-19 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 基因體暨蛋白體醫學研究所 | zh_TW |
| Appears in Collections: | 基因體暨蛋白體醫學研究所 | |
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| U0001-1009202216190300.pdf Restricted Access | 14.42 MB | Adobe PDF |
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