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dc.contributor.advisor謝佳倩zh_TW
dc.contributor.advisorChia-Chien Hsiehen
dc.contributor.author范揚舜zh_TW
dc.contributor.authorYang-Shun Fanen
dc.date.accessioned2025-09-17T16:13:10Z-
dc.date.available2025-09-18-
dc.date.copyright2025-09-17-
dc.date.issued2025-
dc.date.submitted2025-08-08-
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/99635-
dc.description.abstract乳癌是全球女性最常見的惡性腫瘤之一。天然物具有多元的生理活性且低毒性副作用,已廣泛被研究於化學預防。其中lunasin是一具有生物活性的種子胜肽,其作用包括抗腫瘤;近年健康意識抬頭,改變生活型態預防疾病成為主流,其中飲食限制也備受關注,研究顯示短期禁食也可抑制癌細胞的生長。本研究欲探討lunasin與間歇性禁食 (short-term starvation, STS) 處理對於乳癌細胞生長的影響機制。實驗包含兩部分,第一部分為lunasin處理兩株乳癌細胞MCF-7與MDA-MB-231與一株正常乳腺上皮細胞MCF-10A,結果顯示lunasin可抑制MCF-7細胞之乳酸與ATP生成之趨勢,由於效應未達顯著,無法推斷透過瓦式效應。因此第二部分加入STS設計,以期提高抗癌的效果作用,分組為lunasin或STS或兩者合併處理乳癌細胞。首先建立與使用的禁食條件,在低葡萄糖培養基 (1 g/L 葡萄糖,1% FBS) 中相較於無葡萄糖培養基 (0 g/L 葡萄糖,1% FBS),lunasin、STS與合併處理相較控制組,顯著降低兩株乳癌細胞的生長,但不影響正常細胞生長,因此選擇低糖培養基進行後續實驗。在乳癌細胞乳酸及ATP生成結果,lunasin與STS處理後沒有顯著差異,且合併組也未能有協同效應,主要變化是來自於STS的營養缺乏而非lunasin。而在轉錄體分析中,兩株乳癌細胞在STS組及合併處理組對轉錄體表現的影響皆較lunasin組顯著,顯示營養缺乏為主要影響因素。在Gene Set Enrichment Analysis (GSEA) 分析中,乳癌細胞於STS組中顯著富集細胞週期、轉錄後修飾、蛋白質合成及核輸送等路徑。根據上述,lunasin及STS處理對抑制乳癌細胞乳酸與ATP的生成效果有限,而合併處理也未展現協同效應。在轉錄體層面,STS處理是抑制乳癌細胞生長的主要因素,透過比對熱點圖篩選出具潛力的關鍵調控基因,提供未來研究相關機制的標的。zh_TW
dc.description.abstractBreast cancer is the most common cancer among women worldwide. Natural compounds with bioactivity and low toxicity are widely studied for cancer prevention. Lunasin, a bioactive seed peptide, has demonstrated anti-tumor properties. In recent years, lifestyle interventions such as dietary restriction have gained attention for disease prevention. Short-term starvation (STS) has been shown to inhibit cancer cell growth. This study investigated the effects and mechanisms of lunasin and STS on breast cancer cell growth. The study included two parts, in the first part, breast cancer cells MCF-7, MDA-MB-231 and normal breast epithelial cell MCF-10A were treated with lunasin. The results showed that lunasin slightly reduced lactate and ATP production in MCF-7 cells; however, the effects can’t support inhibition of the Warburg effect. Therefore, STS was added in the second part to enhance potential anti-cancer activity. Cells were treated with lunasin, STS, or combination treatment. Low-glucose STS (1 g/L glucose with 1% FBS) was selected based on its ability to inhibit the growth to both cancer cell lines without affecting normal cells. However, lactate and ATP levels weren't significantly different, and no synergistic effect in combination treatment, suggesting that the metabolic effects were primarily driven by STS. Transcriptome analysis revealed that STS induced most of the transcriptional changes, with little added effect from lunasin. GSEA results showed significant enrichment pathways related to cell cycle, post-transcriptional modification, protein synthesis and nucleocytoplasmic transport in STS-treated groups. In conclusion, lunasin and STS treatment had limited effects on lactate and ATP production in breast cancer cells, and no synergistic in combination treatment. Additionally, no glycolysis-related pathways were enriched in the transcriptomic data. STS appeared to be the major contributor to growth inhibition in transcriptional level. Potential regulatory genes were identified from heatmap, offering targets for future mechanistic studies.en
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dc.description.tableofcontents摘要 i
Abstract ii
目次 iii
圖次 vi
表次 vii
第一章、 文獻探討 1
第一節、 乳癌 1
一、 流行病學與臨床分類 1
二、 罹患乳癌的危險因子 2
三、 治療方式 3
第二節、 癌症之代謝重整 4
一、 癌症的特徵 4
二、 癌細胞之醣類代謝 4
三、 癌細胞之脂類代謝 6
四、 Glutamine代謝異常 6
五、 粒線體功能受損 7
第三節、 飲食調整對癌症發展的影響 9
一、 飲食調整之概念與應用 9
二、 飲食干預策略 9
三、 短期飢餓 (short-term starvation, STS) 10
四、 STS與乳癌相關研究 11
五、 STS與Warburg effect 11
第四節、 天然植化素與乳癌 12
一、 飲食因子與癌症 12
二、 Lunasin簡介 12
三、 Lunasin的抗癌活性 13
四、 Lunasin的抗發炎及抗氧化活性 14
五、 其他植化素與乳癌 15
六、 植化素與Warburg effect 16
第二章、 實驗動機與實驗設計 17
第一節、 研究動機與假說 17
第二節、 實驗架構 18
第三章、 實驗材料與方法 19
第一節、 實驗儀器設備 19
一、 實驗室儀器設備 19
二、 拋棄式無菌耗材 19
第二節、 實驗材料與方法 20
一、 細胞培養 20
二、 短期禁食 21
三、 細胞之存活率測驗 21
四、 細胞之葡萄糖攝取 22
五、 細胞之乳酸生產試驗 22
六、 細胞之ATP生產試驗 23
七、 RNA抽取 24
八、 RNA定序分析 25
九、 統計分析 26
第五章、 實驗結果 27
第一節、 Lunasin單獨處理對乳癌細胞生長之影響 27
第二節、 Lunasin單獨處理對乳癌細胞葡萄糖代謝之影響 29
第三節、 建立乳癌細胞短期禁食的實驗條件 31
第四節、 Lunasin、短期禁食與合併處理對乳癌細胞葡萄糖代謝之影響 33
第五節、 Lunasin、短期禁食與合併處理對乳癌細胞轉錄體之影響 35
第六章、 討論 46
第一節、 Lunasin單獨處理對乳癌細胞葡萄糖代謝之影響 46
第二節、 Lunasin、短期禁食與合併處理對乳癌細胞存活率及葡萄糖代謝之影響 47
第三節、 Lunasin、短期禁食與合併處理對乳癌細胞轉錄體之影響 48
一、 乳癌細胞之GSEA分析 48
第七章、 結論 50
第八章、 參考文獻 51
第九章、 附錄 58
第一節、 Lunasin、短期禁食與合併處理對乳癌細胞轉錄體之ORA分析 58
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dc.language.isozh_TW-
dc.subjectLunasinzh_TW
dc.subject短期禁食zh_TW
dc.subject乳癌zh_TW
dc.subject瓦式效應zh_TW
dc.subjectRNA定序分析zh_TW
dc.subject細胞週期zh_TW
dc.subjectbreast canceren
dc.subjectLunasinen
dc.subjectcell cycleen
dc.subjectRNA-sequencingen
dc.subjectWarburg effecten
dc.subjectSTSen
dc.title以轉錄體分析lunasin胜肽與短期禁食對乳癌細胞之影響zh_TW
dc.titleTranscriptomic analysis of the effects of lunasin peptide and short-term starvation on breast cancer cellsen
dc.typeThesis-
dc.date.schoolyear113-2-
dc.description.degree碩士-
dc.contributor.oralexamcommittee林璧鳳;羅凱尹;吳啟豪zh_TW
dc.contributor.oralexamcommitteeBi-Fong Lin;Kai-Yin Lo;Chi-Hao Wuen
dc.subject.keywordLunasin,短期禁食,乳癌,瓦式效應,RNA定序分析,細胞週期,zh_TW
dc.subject.keywordLunasin,STS,breast cancer,Warburg effect,RNA-sequencing,cell cycle,en
dc.relation.page64-
dc.identifier.doi10.6342/NTU202503758-
dc.rights.note同意授權(限校園內公開)-
dc.date.accepted2025-08-12-
dc.contributor.author-college生命科學院-
dc.contributor.author-dept生化科技學系-
dc.date.embargo-lift2030-08-04-
顯示於系所單位:生化科技學系

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