聚酯型兒茶素A抑制腸癌細胞MMP-9與CCL2之表現進而抑制腸癌細胞轉移

許多已開發國家大腸癌已位居癌症死亡率的前三名，而多半造成癌症死亡的原因是癌症轉移(Cancer metastasis)而非腫瘤本身。由於大腸癌在初期階段通常不會表現明顯症狀，所以多數大腸癌患者確診時其病程都已進入轉移階段。本研究Gelatin zymography初篩的結果顯示聚酯型兒茶素A可能具有抑制腸癌細胞轉移的潛力。除此之外，過去文獻指出烏龍茶中的聚酯型兒茶素A (Theasinensin A, TSA) 具有抗發炎的功效，然而其是否具有抑制腸癌細胞轉移的效果尚未明瞭。因此本篇研究旨在探討聚酯型兒茶素A抑制腸癌細胞轉移之機轉。由於過去的文獻指出MMP-9和CCL2 分別在腸癌轉移的內滲(Intravasation)與外滲(Extravasation)階段扮演重要角色，因此本研究將這兩個分子設為探討腸癌細胞轉移之目標蛋白。實驗結果顯示聚酯型兒茶素A可以有效的抑制由12-O-Tetradecanoylphorbol-13-acetate (TPA) 所誘導之上皮-間質細胞轉換(EMT)、間質-上皮細胞轉換(MET)以及細胞的非貼覆性生長。除此之外，聚酯型兒茶素A可能是透過抑制由TPA所誘導的ERK1/2和p38之磷酸化以及AP-1的活性進而抑制MMP-9 和CCL2的蛋白表現量從而有效地抑制由TPA所誘導的腸癌細胞轉移。綜合各項實驗結果，我們推測聚酯型兒茶素A可能具有抑制腸癌細胞轉移之潛力。

關鍵字

癌症轉移；聚酯型兒茶素A (Theasinensin A) ； MMP-9 ； CCL2

並列摘要

Cancer metastasis, the terminal stage of cancer development, is accounting for approximately 90% of all human cancer mortalities. Previous research have suggested that theasinensin A (TSA) has anti-inflammatory effects; however, its potential for inhibiting colon cancer metastasis remains to be unclear. Therefore, in this research, we focused on investigating the mechanism of inhibitory effects of TSA on TPA-induced colon cancer cell migration. Previous studies report that matrix metalloproteinase-9 (MMP-9) is critical to intravasation and C-C motif ligand 2 (CCL2) is critical to extravasation. In our research, we tried to figure out if TSA can downregulate TPA-induced protein expression and activity of MMP-9 and CCL2 mRNA expression in human colon HT-29 cells. Our results showed that TSA effectively inhibited TPA-induced epithelial-mesenchymal transition (EMT), mesenchymal-epithelial transition (MET), cell anchorage independent growth and cell migration in HT-29 cells. Moreover, TSA may downregulate TPA-induced expression of MMP-9 and CCL2 via inhibiting TPA-induced phosphorylation of ERK1/2 and p38 and AP-1 activation whereby further inhibit cancer cell migration. Based on our findings, we suggested that TSA could be a potential compound for preventing colon cancer metastasis.

並列關鍵字

Cancer metastasis ； theasinensin A (TSA) ； matrix metalloproteinase-9 (MMP-9) ； C-C motif ligand 2 (CCL2)

參考文獻

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聚酯型兒茶素A抑制腸癌細胞MMP-9與CCL2之表現進而抑制腸癌細胞轉移

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