Decursin and Decursinol from Angelica gigas Inhibit the Lung Metastasis of Murine Colon Carcinoma
Decursin and Decursinol from Angelica gigas Inhibit the Lung Metastasis of Murine Colon Carcinoma
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DOI：
10.1002/ptr.3372
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发表时间：
2011-07-01
影响因子：
7.2
通讯作者：
Chung, Won-Yoon
中科院分区：
文献类型：
--
作者：
Son, Seung Hwa;Park, Kwang-Kyun;Chung, Won-Yoon
本研究的主要目的是评价从当归中分离出的下丘脑素和下丘脑醇的抗肿瘤活性。地塞米松和地塞米松对CT-26结肠癌细胞的增殖和侵袭均有抑制作用。细胞中基质金属蛋白酶(MMP2)和MMP9的表达及细胞培养上清液中基质金属蛋白酶(MMP2)和MMP9的活性也受到抑制。在CT-26细胞中，细胞外信号调节激酶(ERK)抑制剂抑制细胞增殖、侵袭和基质金属蛋白酶-9的表达，c-jun氨基末端激酶(JNK)抑制剂抑制这两种MMPs的表达，并抑制细胞增殖和侵袭。磷脂酰肌醇-3激酶(PI3K)抑制剂仅减少基质金属蛋白酶-2的表达。另外，抗基质金属蛋白酶-9抗体对CT-26细胞的侵袭有抑制作用，而抗基质金属蛋白酶-2抗体的作用不明显。这些结果表明，通过ERK和JNK途径表达的基质金属蛋白酶-9在CT26细胞的侵袭中起着关键作用。Decursin和Decursinol下调ERK和JNK的磷酸化。此外，口服降钙素和降钙素可减少肺部肿瘤结节的形成和CT-26转移引起的肺重量增加。因此，下丘脑素和下丘脑醇都可能是有益的抗转移药物，靶向MMPs及其上游信号分子。版权所有(C)2011 John Wiley&Sons，Ltd.
The principal objective of the present study was to evaluate the antimetastatic activity of decursin and decursinol isolated from Angelica gigas. Decursin and decursinol inhibited the proliferation and invasion of CT-26 colon carcinoma cells. The expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in cells and the activities in the culture medium were also reduced by decursin and decursinol treatment. In CT-26 cells, the extracellular signal-regulated kinase (ERK) inhibitor inhibited cell proliferation, invasion and MMP-9 expression, and the c-Jun N-terminal kinase (JNK) inhibitor suppressed the expression of both MMPs, as well as cell proliferation and cell invasion. The phosphatidylinositol-3 kinase (PI3K) inhibitor reduced only the expression of MMP-2. In addition, the invasion of CT-26 cells was inhibited by the treatment with anti-MMP-9 antibody, rather than anti-MMP-2 antibody. These results indicate that MMP-9 expression via ERK and JNK plays a critical role for the invasion of CT26 cells. Decursin and decursinol downregulated ERK and JNK phosphorylation. Moreover, oral administration of decursin and decursinol reduced the formation of tumor nodules in the lungs and the increase in lung weight caused by CT-26 metastases. Therefore, both decursin and decursinol may be beneficial antimetastatic agents, targeting MMPs and their upstream signaling molecules. Copyright (C) 2011 John Wiley & Sons, Ltd.