聯合國世界衛生組織指出乳癌是目前全球女性發生率最高的癌症；但是現行的乳癌化療藥物仍有副作用的疑慮，而且對於三陰性的乳癌細胞尚未有有效藥物。近來有學者提出補充和替代醫學(CAM)；希望藉由天然物加強藥物效果，降低副作用，甚至於取代藥物。
有文獻研究天然物-黃酮類化合物抑制癌症的作用機制，並證明quercetin (Que)和沒食子酰基抑制癌症的機制不同。因此我們選用了Que和三種沒食子醯基結構相似物：gallic acid(GA)、(-)-epigallocatechin gallate (EGCG)和1,2,3,4,6-penta-O-galloyl-β-D-Glucose(5GG)在乳癌細胞株中併用，研究是否更有抑制癌細胞生長效果。我們做了細胞存活率、癌化程度、細胞週期停滯、細胞凋亡等相關實驗，皆證實在三陰性的MDA-MB-231細胞株中，Que併用EGCG或5GG皆有協同抑制癌細胞的效果；其中以Que併用5GG抑制癌細胞存活率的效果更為顯著，我們推測可能與5GG含有較多沒食子醯基結構有關。Que併用5GG於短時間二十四小時促使MDA-MB-231細胞細胞週期停滯、長時間四十八小時則細胞凋亡；且由實驗證明能抑制cullin 1、CDK4與SKP2蛋白質。而先前研究得知SKP2可以調控細胞週期的S期，且近來研究亦指出SKP2可能跟細胞凋亡有關，所以我們針對SKP2接續研究細胞停滯與凋亡的相關機制。我們抑制SKP2的表現後，發現因此而使MDA-MB-231細胞產生染色質皺縮、活化細胞凋亡相關蛋白、DNA片斷化等細胞凋亡現象；由此可證SKP2不只可以調控細胞週期亦能調控細胞凋亡。
由本實驗證明Que併用5GG能有效抑制MDA-MB-231細胞增生，我們希望未來能進一步地研究Que併用5GG對於癌症轉移、體內試驗的效果，更甚至併用或是替代臨床藥物。

　　Breast cancer is the most universal cancer in women, but the medications of breast cancer usually cause serious side effects and is no effective treatment for triple-negative breast cancer. Therefore, we wanted to use complementary and alternative medicine (CAM) for reducing the side effects and improving breast cancer treatment. Previous studies showed that the flavonoids quercetin (Que) was a natural product and could inhibit cancer cell growth and the anti-cancer mechanisms of Que was different from galloyl moiety structural analogs. For the reason that we wanted to examine the effect of breast cancer cells co-treated with Que plus GA, EGCG, or 5GG respectively. We found that Que combined with 5GG was most effective in inhibiting triple-negative breast cancer, MDA-BM-231, cell growth.
　　We discovered that combined treatment with Que and 5GG induced cell cycle arrest and apoptosis at different time points, and decreased the protein expressions of cullin 1, CDK4, and SKP2. After SKP2 siRNA transfection for 48 hours, MDA-MB-231 cells showed more apoptotic cells. It has been known that Skp2 plays an important role in regulating G1–S-phase progression. In the present study, we conjectured that RNAi knockdown of SKP2 not only induced cell cycle arrest but also induced apoptosis in MDA-MB-231 cells. Additionally, phosphorylated AKT expression was present at low levels in MDA-MB-231 co-treated with Que and 5GG. We suggested that co-treated with Que and 5GG inhibited MDA-MB-231 cells growth through suppression of the PI3K/Akt pathway. Thus, the combination of Que and 5GG warrants further study as a potential treatment for breast cancer.

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