篇名 | 烏龍茶成分Theasinensin A可透過調降MMP-9與CCL2抑制12-O-Tetradecanoylphorbol-13-acetate所誘導HT-29腸癌細胞株之轉移活性 |
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卷期 | 58:4/5 |
並列篇名 | Theasinensin A Exerts Anti-metastatic Effects on HT-29 Cells via Downregulating the Expression of MMP-9 and CCL2 |
作者 | 李佳軒 、 林偉盛 、 楊美珠 、 何其儻 、 潘敏雄 |
頁次 | 127-137 |
關鍵字 | 癌症轉移 、 聚酯型兒茶素A 、 基質金屬蛋白酶9 、 趨化素配體2 、 Cancer metastasis 、 theasinensin A 、 matrix metalloproteinase-9 、 C-C motif ligand 2 、 Scopus 、 TSCI |
出刊日期 | 202010 |
DOI | 10.6578/TJACFS.2020010_58(4_5).0004 |
癌症長年位居我國十大死因之首,亦是許多已開發國家主要死因,而在所有癌症中結腸直腸癌死亡率高居第二,由於結腸直腸癌在初期階段病症不易察覺,因此當診斷並開始接受治療時,大腸癌患者其病程都已進入轉移階段,此時已很難根除,因此大腸癌患者死亡的主因為癌症轉移 (cancer metastasis) 而非腫瘤本身。Theasinensin A是烏龍茶中主要的聚酯型兒茶素,為EGCG之二聚體。研究已經指出Theasinensin A具有抗氧化、抗發炎、誘發癌細胞凋亡等生物活性。本研究初步透過明膠蛋白酵素電泳法分析發現Theasinensin A可能具有抑制腸癌細胞轉移的潛力,後續進一步探討Theasinensin A是否具抑制12-O-Tetradecanoylphorbol-13-acetate (TPA) 誘導腸癌細胞HT-29轉移之能力與相關分子機制。MMP-9與CCL2兩者對於腸癌轉移的內滲 (intravasation) 與外滲 (extravasation) 階段扮演重要角色,本研究以兩者之表達作為腸癌細胞轉移之目標蛋白。結果顯示, Theasinensin A可以有效的抑制由TPA所誘導之上皮-間質細胞轉換 (epithelial to mesenchymal transition, EMT)、間質-上皮細胞轉換 (mesenchymal to epithelial transition, MET) 及細胞的非貼覆性生長。此外,Theasinensin A可能透過抑制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。綜上所述,Theasinensin A可能具有抑制腸癌細胞轉移之潛力。
Cancer metastasis, the terminal stage of cancer development, is accounting for approximately 90% of all human cancer mortalities. Previous research has 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 show that matrix metalloproteinase-9 (MMP-9) and C-C motif ligand 2 (CCL2) are critical factors that cause cancer cell intravasation and 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. Our findings suggested that TSA could be a potential compound for preventing colon cancer metastasis.