乳癌是全球女性最常見的惡性腫瘤，也是女性癌症死因的第一名。癌細胞轉移是導致乳癌患者死亡的主因。Twist-1屬於basic-helix-loop-helix (bHLH)家族轉錄因子，已被證實在啟動上皮細胞間質化(Epithelial-mesenchymal transition, EMT)，促進多種癌細胞移行和侵襲作用扮演關鍵角色。先前研究證實n-3 PUFAs對於抑制乳癌發展有顯著效果，然而對於抑制三陰性乳癌細胞轉移機制仍不清楚。本研究以Hs578T三陰性乳癌細胞實驗模式，探討次亞麻油酸(α-linolenic acid, 18:3, n-3; ALA)透過何種機制影響癌細胞EMT和轉移。結果顯示：預處理100 μM ALA顯著抑制Twist-1蛋白質表現。處理ALA或利用siRNA將Twist-1基因knockdown後皆可顯著抑制乳癌細胞移行能力。處理ALA 60 min後可顯著抑制p-STAT3α蛋白質表現。一旦將STAT3α基因knockdown後亦可抑制twist-1、N-cadherin蛋白質表現。預處理ALA或twist-1 siRNA可增加上皮標誌物E-cadherin蛋白質表現並顯著抑制twist-1、snail2、N-cadherin、vimentin、fibronection等間質標誌物蛋白質表現。綜合上述實驗結果，ALA可透過負向調控STAT3α表現及活性抑制twist-1表現，進而抑制乳癌細胞間質化並降低三陰性乳癌細胞移行。
Breast cancer is the commonly diagnosed cancer among women all over the world. Metastasis is leading cause of death from breast cancer. Twist-1 is a basic-helix-loop-helix (bHLH) transcription factor essential in embryological morphogenesis. Several studies showed that Twist-1 plays an important role in cancer cell epithelial-mesenchymal transition (EMT), migration and invasion. Previous studies showed thatn-3 PUFAs was observed to display anticancer activity on in breast cancer, however, the anti-metastatic mechanism of n-3 PUFAs for triple-negative breast cancer cells is still unclear. In this study, we investigated the effect of ALA on cell EMT and metastasis on Hs578T TNBC cells We found that 100 μM ALA significantly inhibited Twist-1 expression. Cell migration was suppressed by ALA or Twist-1 siRNA treatment. Treatment with ALA for 60 min significantly inhibited the phosphorylation of STAT3α. Upon STAT3α knockdown, the protein level of twist-1 and N-cadherin were decreased. Pretreatment with ALA or Twist-1 siRNA, increasedthe epithelial marker such as E-cadherin protein expression and decreased the mesenchymal markers including twist-1, snail2, N-cadherin, vimentin, fibronection protein expression. Taken together, our result indicate that ALA suppressed EMT and cell migration may through down-regulation of STAT3α expression and activity as well as twist-1 expression on Hs578T triple-negative breast cancer cells.
