Department of Surgery, The Second Affiliated Hospital of Wenzhou Medical College, No. 109, West Xue-yuan Road, Wenzhou 325027, PR China.
Oncol Rep. 2011 Jul;26(1):81-9. doi: 10.3892/or.2011.1257. Epub 2011 Apr 12.
Emodin (1, 3, 8-trihydroxy-6-methylanthraquinone) is an active constituent isolated from the root of Rheum palmatum L and is the main effective component of some Chinese herbs and plants. Pharmacological studies have demonstrated that emodin exhibits anti-cancer effects on several human cancers. However, the molecular mechanisms of emodin-mediated tumor regression have not been fully defined. This study was performed to investigate the antiproliferative and antimetastatic effects of emodin on pancreatic cancer in vitro and in vivo. Our results showed that emodin induced a higher percentage of growth inhibition and apoptosis in the pancreatic cancer cell line SW1990 compared to that of control, and emodin suppressed the migration and invasion of SW1990 cells in a dose-dependent manner. To investigate the possible mechanisms involved in these events, we performed electrophoretic mobility shift assay (EMSA) and Western blot analysis, and found that emodin significantly down-regulated NF-κB DNA-binding activity, survivin and MMP-9 in SW1990 cells. Moreover, the expression of cleaved caspase-3 was up-regulated in SW1990 cells after treatment with emodin. In addition, a metastatic model simulating human pancreatic cancer was established by orthotopic implantation of histologically intact human tumor tissue into the pancreatic wall of nude mice. Oral administration of emodin significantly decreased tumor weight and metastasis compared to control. Furthermore, the expression of NF-κB, survivin and MMP-9 were also suppressed in tumor tissues after treatment with emodin. Collectively, our results indicated that emodin exerts antiproliferative and antimetastatic activity on pancreatic cancer both in vitro and in vivo, which may be related to down-regulation of NF-κB and its regulated molecules such as survivin and MMP-9 proteins. Consequently, these results provide important insights into emodin as an anti-invasive agent for the therapy of human pancreatic cancer.
大黄素（1,3,8-三羟基-6-甲基蒽醌）是从大黄根中分离得到的一种活性成分，是一些中草药的主要有效成分。药理研究表明，大黄素有抗多种人类癌症的作用。然而，大黄素介导的肿瘤消退的分子机制尚未完全确定。本研究旨在探讨大黄素在体外和体内对胰腺癌的增殖抑制和抗转移作用。我们的结果表明，与对照组相比，大黄素诱导的胰腺癌细胞系 SW1990 的生长抑制和凋亡比例更高，大黄素以剂量依赖性方式抑制 SW1990 细胞的迁移和侵袭。为了探讨涉及这些事件的可能机制，我们进行了电泳迁移率变动分析（EMSA）和 Western blot 分析，发现大黄素显著下调了 SW1990 细胞中的 NF-κB DNA 结合活性、survivin 和 MMP-9。此外，大黄素处理后 SW1990 细胞中 cleaved caspase-3 的表达上调。此外，通过将组织学完整的人肿瘤组织原位植入裸鼠胰腺壁建立了模拟人类胰腺癌转移的模型。与对照组相比，口服大黄素可显著降低肿瘤重量和转移。此外，大黄素处理后肿瘤组织中 NF-κB、survivin 和 MMP-9 的表达也受到抑制。总之，我们的结果表明，大黄素在体外和体内均对胰腺癌具有增殖抑制和抗转移作用，这可能与下调 NF-κB 及其调节分子如 survivin 和 MMP-9 蛋白有关。因此，这些结果为大黄素作为人类胰腺癌治疗的侵袭抑制剂提供了重要的见解。
