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

張佳心(Chang Chia-Hsin)

指導教授 ： 謝佳倩

國立臺灣師範大學/理學院/營養科學碩士學位學程/碩士(2020年)

https://doi.org/10.6345/NTNU202001486

摘要

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。

關鍵字

Lunasin ； 乳癌 ； 雌激素 ； 芳香酶 ； 發炎

並列摘要

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.

並列關鍵字

Lunasin ； Breast cancer ； Estrogen ； Aromarase ； Inflammation

參考文獻

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