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研究生: 張佳心
Chang, Chia-Hsin
論文名稱: Lunasin對MCF-7與MDA-MB-231人類乳癌細胞生長機制之探討
The effects of lunasin on the mechanism of cell growth in MCF-7 and MDA-MB-231 human breast cancer cells
指導教授: 謝佳倩
Hsieh, Chia-Chien
學位類別: 碩士
Master
系所名稱: 營養科學碩士學位學程
Graduate Program of Nutrition Science
論文出版年: 2020
畢業學年度: 108
語文別: 中文
論文頁數: 102
中文關鍵詞: Lunasin乳癌雌激素芳香酶發炎
英文關鍵詞: Lunasin, Breast cancer, Estrogen, Aromarase, Inflammation
DOI URL: http://doi.org/10.6345/NTNU202001486
論文種類: 學術論文
相關次數: 點閱:177下載:0
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  • 癌症為全球死因之首,其中乳癌為女性最常見的癌症種類。流行病學研究發現肥胖為乳癌的危險因子之一,會使身體產生慢性發炎的環境,肥胖的促炎因子也會增加體內芳香酶活性及發炎基因表現量,促使雌激素濃度上升,加速乳癌惡化,雌激素更是停經後婦女誘導乳癌惡化的危險因子之一。Lunasin是一種分子量為5.5 kDa的種子胜肽,由43個胺基酸所組成,研究證實lunasin具有抗氧化、抗發炎、抗癌及降膽固醇等功效,而lunasin對於乳癌細胞的發炎基因表現、細胞激素等調控機制尚未明確,因此本研究欲探討,lunasin是否能藉由調節發炎因子、雌激素受器與芳香酶表現,進而抑制乳癌細胞生長。為了解lunasin對雌激素依賴性MCF-7及非雌激素依賴性MDA-MB-231乳癌細胞影響,以及在雌二醇 (Estradiol, E2)模式下lunasin是否能有效抑制乳癌細胞之生長,進而測試lunasin處理對細胞存活率、發炎基因及細胞激素分泌調控、芳香酶濃度等影響,及E2模式下細胞存活率、細胞活性、細胞週期及細胞凋亡的影響。第一部分為探討lunasin介入對乳癌細胞之影響,結果顯示 l unasin處理顯著抑制兩株乳癌細胞的存活率,而對MCF-10A正常細胞則無細胞毒性,並能降低所有細胞的芳香酶活性及基因表現、抑制ERα基因。在MDA-MB-231細胞方面,lunasin可以降低VEGF濃度和細胞活性,並可增加ERβ及IL-6基因表現及增加MDA-MB-231細胞其細胞凋亡等等 。第二部分為探討雌激素模式下lunasin介入對乳癌細胞之影響,結果顯示E2能顯著增加MCF-7細胞之細胞存活率,而lunasin在E2模式下依舊保有抑制兩株乳癌細胞其細胞存活率之效果,且能降低MCF-7細胞其細胞活性。綜觀上述,lunasin可以藉由降低細胞存活率、促炎基因表現、調控發炎性細胞激素濃度、降低芳香酶活性及增加細胞凋亡等,抑制乳癌腫瘤細胞的生長,因此富含lunasin的飲食可能有助於對乳癌的預防及患者的輔助治療。

    Cancer is the leading cause of death worldwide, and breast cancer is the most common type of cancer in women. Epidemiological studies have found that the women with overweight or obesity have higher risk developed breast cancer. The Pro-inflammatory factors of obesity can also increase aromatase activity and inflammatory gene expression in the body, which induces the increase of estrogen concentration and causes estradiol overproduction and also accelerates the deterioration of breast cancer. Estrogen is one of the risk factors for the worsening of breast cancer in postmenopausal women. Lunasin is a seed peptide which consist of 43 amino acids. Studies have confirmed that lunasin has antioxidant, anti-inflammatory, chemoprevention and anti-cancer. However, the effect of lunasin on inflammatory gene expression, cytokines, estrogen receptor and aromatase expression in breast cancer cells has no clear. The aim of this study is intended to find out the whether lunasin can inhibit the growth of MCF-7 and MDA-MB-231 breast cancer cells by regulation of inflammatory factors, estrogen receptor and aromatase expression, and whether lunasin can effectively inhibit the growth of breast cancer cells in the estradiol(E2)-related microenvironment. The first part is to find out the effect of lunasin intervention on breast cancer cells. The results show that lunasin treatment can significantly inhibit the cell viability of breast cancer cells, and can reduce aromatase activity and gene expression, inhibition of all cells ERα gene, reduce the VEGF concentration and cell activity of MDA-MB-231 cells. Furthermore, lunasin can increase the trend of ERβ and IL-6 gene expression and increase the apoptosis of MDA-MB-231 cells. The second part is to investigate the effect of lunasin treat on breast cancer cells in the E2-related microenvironment. The results show that E2 can significantly increase the cell viability of MCF-7 cells, while lunasin still inhibits the cell viability of breast cancer cells in E2-related microenvironment. In addition, lunasin can reduce the cell vitality MCF-7 cells. In summary, lunasin can inhibit the growth of breast cancer cells by reducing cell viability, pro-inflammatory gene expression, regulating the concentration of inflammatory cytokines, reducing aromatase activity, and increasing breast cancer cells apoptosis. Therefore, the diet rich in lunasin may have contribute to the prevention of breast cancer and be a promising adjuvant therapy to related breast cancer.

    第一章、文獻探討 1 第一節、乳癌 1 一、乳癌的流行病學與臨床分類 1 二、乳癌與肥胖 2 三、乳癌與雌激素 7 四、乳癌與芳香酶 9 五、乳癌與植物化學成分 10 第二節、Lunasin 13 一、Lunasin簡介 13 二、Lunasin抗腫瘤作用 14 三、Lunasin抗發炎及抗氧化作用 16 四、其他 17 第二章、研究動機與目的 19 第一節、動機與假說 19 第二節、實驗架構圖 20 第三章、實驗材料與方法 21 第一節、實驗藥品來源 21 第二節、實驗細胞來源 21 第三節、實驗儀器設備耗材 21 第四節、實驗材料與方法 22 一、細胞培養 22 (一)MCF-7人類乳癌細胞 22 (二)MDA-MB-231人類乳癌細胞 22 (三)3T3-L1小鼠纖維母細胞 22 (四)MCF-10A人類正常乳腺細胞 22 二、Lunasin處理對人類乳癌細胞、乳腺細胞及小鼠脂肪纖維母細胞生長之影響 23 (一)細胞存活率試驗 23 三、Lunasin處理對人類乳癌細胞、乳腺細胞發炎相關因子之影響 24 (一)基因表現量測定:逆轉錄聚合酶鏈式反應 24 (二)細胞激素測定:酵素免疫分析法 27 四、Lunasin處理對人類乳癌細胞、乳腺細胞及小鼠脂肪纖維母細胞芳香酶活性之影響 30 (一)3T3-L1小鼠纖維母細胞分化與未分化之芳香酶活性比較 30 (二)Lunasin處理對3T3-L1小鼠纖維母細胞芳香酶活性之影響 32 (三)Lunasin處理對人類乳癌細胞及乳腺細胞芳香酶活性之影響 32 五、雌激素介入下lunasin處理對人類乳癌細胞與乳腺細胞之影響 33 (一)雌激素模式下之細胞存活率試驗 33 (二)雌激素模式下lunasin處理之細胞存活率試驗 33 (三)細胞活性試驗 33 (四)細胞凋亡試驗 34 (五)細胞週期試驗 35 第五節、統計分析 36 第四章、實驗結果 37 第一節、Lunasin處理對細胞生長之影響 37 第二節、Lunasin處理對發炎相關因子之影響 41 一、Lunasin處理對人類乳癌細胞與乳腺細胞之發炎基因與細胞激素分泌之時間相關性分析 41 二、Lunasin處理對人類乳癌細胞與乳腺細胞發炎相關基因之影響 45 三、Lunasin處理對人類乳癌細胞與乳腺細胞其細胞激素分泌之影響 47 第三節、Lunasin處理對細胞芳香酶活性之影響 49 一、3T3-L1小鼠纖維母細胞其細胞存活率與芳香酶活性之影響 49 二、lunasin處理對人類乳癌細胞與乳腺細胞芳香酶活性之影響 52 第四節、雌激素模式下lunasin處理對乳癌細胞與乳腺細胞之影響 54 一、雌激素處理對人類乳癌細胞與乳腺細胞存活率之影響 54 二、雌激素模式下lunasin處理對人類乳癌細胞與乳腺細胞其細胞存活率之影響 56 三、雌激素模式下lunasin處理對人類乳癌細胞與乳腺細胞其細胞活性之影響 59 四、雌激素模式下lunasin處理對人類乳癌細胞與乳腺細胞其細胞凋亡之影響 63 五、雌激素模式下lunasin處理對人類乳癌細胞與乳腺細胞其細胞週期之影響 66 第五章、討論 68 第一節、Lunasin處理對對人類乳癌及乳腺細胞生長之影響 68 一、lunasin處理對人類乳癌及乳腺細胞其細胞存活率之影響 68 二、lunasin處理對人類乳癌及乳腺細胞細胞活性及細胞凋亡之影響 69 三、lunasin處理對人類乳癌及乳腺細胞其細胞週期之影響 70 第二節、Lunasin處理對發炎相關因子之影響 72 一、Lunasin處理對人類乳癌及乳腺細胞發炎相關基因表現之影響 72 二、Lunasin處理對人類乳癌及乳腺細胞發炎性細胞激素分泌之影響 73 第三節、雌激素模式下lunasin對乳癌細胞之影響 76 一、Lunasin處理對細胞芳香酶活性之影響 76 二、雌激素模式下lunasin處理對人類乳癌及乳腺細胞其細胞活性、細胞凋亡與細胞週期之影響 77 第六章、結論 79 附錄 82 參考資料 86

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