鞣花酸減少腎臟癌細胞移動和侵襲能力是經由抑制基質金屬蛋白酵素-1的表現

腎臟癌中最常見的是腎細胞癌(Renal cell carcinoma, RCC)，由於腎細胞癌早期較沒有明顯的臨床症狀，通常診斷出來都為中、晚期了，加上腎細胞癌有高度的轉移能力，在治療上相對困難。鞣花酸(Ellagic acid, EA)是存在於眾多水果和蔬菜中的天然的抗氧化劑，是屬於多酚類的一員，也在多篇研究中證實鞣花酸具有抗氧化、抗糖尿病、抗癌和誘導細胞凋亡的活性，例如在非小細胞肺癌、胰臟癌、乳癌等等，鞣花酸經由不同的路徑，進而去抑制腫瘤的生長，目前鞣花酸對於腎臟癌還沒有太多的文獻研究，所以想探討鞣花酸對於腎細胞癌的作用機制。實驗結果顯示在不同濃度的鞣花酸不抑制786-O和ACHN腎細胞癌的細胞生長和細胞週期改變，然而對於786-O和ACHN腎細胞癌移動和侵襲能力都有顯著的抑制效果，接下來檢測基質金屬蛋白酵素相關蛋白的表現，實驗證實鞣花酸抑制基質金屬蛋白酵素-1 (Matrix metalloproteinase-1, MMP-1) mRNA表現量，但不影響其它基質金屬蛋白酵素表現。藉由TISIDB資料庫的分析結果證實腎臟癌病患內的MMP-1的表現比起正常人更有顯著的增加。為了了解MMP-1在鞣花酸抑制腎細胞癌移動和侵襲的角色，我們採用重組蛋白MMP-1合併鞣花酸發現重組蛋白MMP-1回復鞣花酸抑制腎細胞癌移動和侵襲能力。此項研究說明鞣花酸抑制腎細胞癌移動和侵襲是透過MMP-1的轉錄和轉譯作用，未來可以再進一步去了解鞣花酸對於MMP-1轉錄調控機制，並且加以了解相關訊息傳遞。

The most common type of kidney cancer is renal cell carcinoma (RCC). Due to the lack of obvious clinical symptoms in the early stages, RCC is usually diagnosed in the middle to late stages. Additionally, kidney cancer cells have a high ability to metastasize, making treatment relatively difficult. Ellagic acid (EA) is a natural phenolic antioxidant found in many fruits and vegetables. Several studies have confirmed that EA has antioxidant, anti-diabetic, anti-cancer, and apoptosis-inducing activities, which can inhibit tumor growth. Currently, there is not much literature on the effects of EA on kidney cancer, so the study will explore the mechanism of ellagic acid on renal cell carcinoma. In this experiment, two cell lines of renal cancer cells, 786-O and ACHN, were used for cell culture to investigate the change ability of migration and invasion of renal cancer cells under treatment with different concentrations of EA. Real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR ) and Western blotting were used to detect the expression of relevant proteins. The results showed that there was no significant difference in the cell cycle of renal cancer cells under treatment with different concentrations of EA. However, there was a significant decrease in the migration and invasion ability of the two cancer cell lines. Further understanding of the expression of matrix metalloproteinases, the results showed both the mRNA and protein expression of matrix metalloproteinase-1 (MMP-1) show significant decreases. From the experimental results, it is known that EA causes a significant decrease in the protein expression and mRNA levels of MMP-1. This indicates that EA can affect the transcriptional activity of MMP-1. Therefore, in the future, we can investigate which promoters EA targets on MMP-1, and to understand through which pathway the upstream signaling is transmitted.