迷迭香酸及肉桂酸對癌細胞生長及侵入轉移抑制功效之動物實驗

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標題:	迷迭香酸及肉桂酸對癌細胞生長及侵入轉移抑制功效之動物實驗 Antiproloferatory and Antimetastastic Effects of Rosmarinic Acid and Cinnamic Acid on Tumor in Animal Model
作者:	高振盛
貢獻者:	保健營養系翁嘉瑞孫芳明
關鍵字:	基質金屬蛋白酶肉桂酸迷迭香酸癌症動物模式 Matrix metalloproteinase Cinnamic acid Rosemary acid Cancer animal model
日期:	2015
上傳時間:	2015-10-21 17:11:23 (UTC+8)
摘要:	惡性腫瘤為全世界常見的致死性疾病。迷迭香酸（Rosmarinic acid, RA）及肉桂酸 (Cinnamic acid, CA) 是植物中萃取的的活性化合物。許多研究顯示，RA 及 CA 可以抑制癌細胞生長。這項研究目的是探討 RA 及 CA 對癌細胞生長及侵入轉移抑制功效之動物試驗。癌細胞皮下移植在三週齡雄性裸鼠。隨機分成七組：控制組（C-），對照組（C+），和 RA 低（1.1 mg/kg）、中（10.8 mg/kg）、高（21.6 mg/kg）劑量組及 t-CA (21.6 mg/kg)、c-CA (21.6 mg/kg) 組，每兩天灌食一次且每週測量體重與腫瘤大小，異種移植後八週犧牲，抽取血液檢測生化值、基質金屬蛋白?-2 及 -9 (Matrix metalloproteinase-2 & -9)，萃取組織蛋白質測定訊息蛋白 (MAPKs pathway、NF-B 及 AP-1) 活性及 MMP-2、-9、TIMP-1、TIMP-2 之mRNA 表現量測定。結果表示，餵食 RA 及 CA 對裸鼠生長並無影響；RA 在 21.6 mg/kg 時腫瘤較其他組別小，且 MMP-2 抑制效果最佳，組織蛋白質中磷酸化 ERK、JNK、p38、NF-B 及 AP-1 均受到抑制，基因表現 MMP-2 及 -9 也受抑制，與過去體外試驗雷同；CA 兩組腫瘤明顯小於對照組，且MMP-2 及 -9 受到抑制，組織蛋白質中磷酸化 ERK、JNK、p38、NF-B 及 AP-1 也受到抑制，基因表現 MMP-2 及 -9 同樣受到抑制，但是兩者間抑制功效差異不大。由上述結果證明 RA 及 CA 在動物試驗中對癌細胞具有生長及侵入轉移之抑制功效。 Malignancies is a kind of worldwide fatal disease . Rosmarinic acid (RA) and cinnamic acid (CA) are active compounds in plants. Many studies indicated that RA and CA can inhibit growth of cancer cells in vitro. This study was further to investigate that RA and CA could suppress proliferation and invasion of cancer cells in vivo. Cancer cells were transplanted into male nude mice of three week old subcutaneously . Experimental mice were randomly divided into seven groups: negative control group (C-), positive control group (C +), RA treated [low (1.1 mg/kg), medium (10.8 mg/kg) , and high (21.6 mg/kg) dose] groups, and CA treated [t-CA (21.6 mg/kg) and c-CA (21.6 mg/kg)] groups. The mice were force-fed once every second day and measured body weight and tumor size weekly. The mice were sacrificed at eight weeks after xenotransplantation. The bloods were used to examine biochemical parameters, matrix metalloproteinase (MMP)- 2 and -9. The tissue proteins were used to analyze molecular signaling (MAPKs pathway, NF-B and AP-1) and mRNA expression of MMP-2, -9, TIMP-1, and TIMP-2. The results showed that the body weights of mice were not affected by feeding RA and CA. The tumor bearing in mice treated with RA at 21.6 mg/kg was smaller than the other groups. Moreover, the activity of MMP-2, the phosphorylation of ERK, JNK, p38, NF-B and AP-1, and the expression of MMP-2 and -9 were also inhibited. The tumors bearing in mice treated with t-CA and c-CA were significantly smaller than the control group. The activities of MMP-2 and -9, the phosphorylation of ERK, JNK, p38, NF-B and AP-1, and the expression of MMP-2 and -9 were also inhibited. From these data, we concluded that RA and CA might be the inhibitors for the growth and invasion of cancer cells.
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