近年來國人的十大死因以惡性腫瘤為首，而肺癌於近幾年漸漸成為惡性腫瘤中主要的死亡原因。癌細胞的轉移往往是造成癌症患者致命的原因之一。癌細胞轉移是一個相當複雜的過程，最重要的是會透過基質金屬蛋白酶(matrix metalloproteinases, MMP)的分解作用達到轉移的目的。MMP-2和MMP-9是可分解細胞外基質(extracellular matrix , ECM) 和基底膜 (basement membranes) 的酵素，因此在癌細胞轉移過程中扮演十分重要的角色。鞣花酸(ellagic acid; EA）是一種存在於蔬果，如：藍莓、草莓和堅果類中的酚類化合物，根據文獻研究指出，鞣花酸可以誘導其細胞凋亡及減少癌症的發生，但目前鞣花酸對於肺癌細胞轉移是否有抑制作用，尚無相關文獻探討，因此本實驗就以鞣花酸來探討對於人類肺癌細胞株A549之轉移的抑制作用及其機制。由細胞附著(cell adhesion)、細胞移行 (cell migration) 及細胞侵入能力(cell invasion) 試驗可看到鞣花酸對於A549的爬行及侵入能力有抑制效果。由明膠蛋白酵素電泳法顯示鞣花酸可減少MMP-2和u-PA的活性。利用西方點墨分析可發現鞣花酸可增加MMP-2的內生性抑制劑TIMP-2的蛋白質表現，同時PAI-1的表現增加，亦能間接讓MMP-2的分泌量減少。因此推論鞣花酸抑制A549轉移是經由抑制MMP-2表現及增加TIMP-2和u-PA的蛋白表現量來達到抑制癌細胞轉移的能力。
Metastasis in cancer patients is often fatal cancer caused by one of the reasons. Metastasis of cancer cells involve multiple processes and various cytophysiological changes, including changing adhesion capability between cells and extracellular matrix (ECM) and damaging intercellular interaction. Degradation of the ECM of the basement membrane was caused by proteinases such as matrix metalloproteinases (MMPs). Among the MMPs family, MMP-2 and MMP-9 play a critical role in tumor invasion and metastasis, therefore, the inhibition of cell migration or invasion mediated by MMP-2 and MMP-9 could be a preventive way of cancer metastasis. Ellagic acid (EA), an antioxidant, is a phenolic compound presenting in fruits (raspberries, blueberries, strawberries) and walnuts. However, the mechanism of EA on the anti-metastasis is still unclear. In this study, EA was used to evaluate growth inhibition, the inhibitory effects of EA on the growth of tumor cells were determined by MTT assay. EA showed an inhibit ory effect on cell migration and invasion by transwell chamber assay. we found that EA can reduce the MMP-2 and urokinase-plasminogen activator (u-PA) activity by zymography and Western-blot. EA also induced the endogenous inhibitor, tissue inhibitors of metalloproteinases (TIMPs) by Western-blot. These findings suggest that EA has potential as an antimetastatic agent.
