以高層次微矩陣分析荳蔻明（Cardamonin）誘發小鼠血癌細胞株WEHI-3的基因表現

Induction of Gene Expression in WEHI-3 Mouse Leukemia Cells by Cardamonin Revealed by Microarray Analysis

邱素琴(Su-Chin Chiu) ； 周建聖(Jiann-Shang Chou) ； 李美慧(Mei-Hui Lee) ； 施勇綸(Yung-Luen Shih) ； 陳媛孃(Yung-Liang Chen) ； 廖年捷(Nien-Chieh Liao) ； 呂旭峰(Hsu-Feng Lu) ； 周沛宜(Pei-Yi Chou) ； 陳國維(Kuo-Wei Chen) ； 薛樹清(Shu-Ching Hsueh)

《檢驗及品保雜誌》 10卷1期 (2021/01) Pp. 1-9

https://doi.org/10.6573/JTQA.202101_10(1).01

摘要

荳蔻明（Cardamonin）屬芳香酮類（aromatic ketones family），被認為與抗菌、抗發炎與抗癌有關，然而有關荳蔻明抗血癌WEHI-3細胞的研究仍然寥寥可數。本研究透過高層次微矩陣（microarray）分析發現荳蔻明可激活數個基因，囊括基因Ly6g（25.8倍），此基因與顆粒白血球的分化與成熟有關。其次為基因Anxa1（9.6倍），此基因與抑制細胞生長與導致細胞凋亡具關連性。其餘被活化的基因如下：Mpeg1（7.7倍）涉及先天免疫系統。S100a4（7.2倍）被認為是觸發癌細胞轉移的基質金屬蛋白酶9（MMP-9）有關。另外還包括Tgm2（7.0倍），被認為與抑制凋亡和促進癌細胞生長有關。Ifi27（6.7倍）所轉譯的蛋白質使細胞週期停滯在S期，導致較低的細胞增殖率。此外也包含與賴氨酸（lysine）的生物合成途徑有關的L-氨基己二酸半醛脫氫酶磷酸轉移酶（alpha-aminoadipate）其活化所涉及的Lys2（6.3倍），而Hsd11b1（6.3倍）與調節糖皮質激素受體（glucocorticoid receptors）有關。除上述基因之外，還強化一些信號轉導，包括：（i）與癌前疾病中的擴增有關的雌激素受體（estrogen receptor）信號轉導；（ii）與調節細胞週期G1／S檢查點相關的訊息傳遞；（iii）與DNA修復有關的Sirtuin信號轉導途徑；（iv）與凋亡有關的芳香烴受體訊息傳遞以及（v）與標記某些蛋白質降解有關的蛋白質泛素化途徑。總之，微陣列的分析可完全理解數百個甚至數千個基因是否被激活或抑制，而無需漫無目地的使用西方墨點進行數以千計的蛋白質篩選。蛋白質篩選。

關鍵字

荳蔻明 ； 芳香酮類 ； 高層次微矩陣分析 ； 糖皮質激素受體

並列摘要

Cardamonin (CAD) is an aromatic ketone. It has anti-bacterial, anti-inflammatory, and anticancer activities. However, its anti-cancer effect has not been well characterized. In this study, we investigated the effect of CAD on the expression of genes in WEHI-3 mouse leukemia cells using microarrays. Results showed that CAD treatment of WEHI-3 cells increased the expression of Ly6g by 25.8 fold, Anxa 1 by 9.6 fold, Mpeg1 by 7.7 fold, S100a4 by 7.2 fold, Tgm2 by 7.0 fold, Ifi27 by 6.7 fold, Lys2 by 6.3 fold, and Hsd11b1 by 6.3 fold. Ly6g is involved in granulocyte differentiation and maturation. Anxa 1 plays a role in the inhibition of cell growth and induction of apoptosis. Mpeg1 is involved in innate immunity. S100a4 activates matrix metalloproteinase 9 and enhances metastasis of cancer cells. Tgm2 inhibits apoptosis and promotes cancer cell growth. Ifi27 mediates cell cycle arrest in the S phase thus reducing cell proliferation. Lys2 activates alpha-aminoadipate dehydrogenase in lysine biosynthesis pathway. Hsd11b1 regulates the activity of glucocorticoid receptors. CAD also activated the following in WEHI-3 cells: (i) Estrogen receptor signaling related to the amplification of precancerous diseases; (ii) G1/S checkpoint regulation associated with cell cycle; (iii) Sirtuin signaling pathway related to DNA repair; (iv) Aryl hydrocarbon receptor signaling associated with apoptosis; and (v) Protein ubiquitination pathway related to proteins degradation. In conclusion, CAD treatment affected the expression of numerous genes in WEHI-3 cells.

並列關鍵字

Cardamonin ； aromatic ketones ； high level microarray ； glucocorticoid receptor