Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Int J Cancer. 2011 Jul 1;129(1):88-100. doi: 10.1002/ijc.25656. Epub 2010 Nov 3.
Cholangiocarcinoma (CCA) is a highly metastatic tumor linked to liver fluke infection and consumption of nitrosamine-contaminated foods and is a major health problem especially in South-Eastern Asia. In search for a suitable chemopreventive agents, we investigated the effect of curcumin, a traditional anti-inflammatory agent derived from turmeric (Curcuma longa), on CCA development in an animal model by infection with the liver fluke Opisthorchis viverrini and administration of N-nitrosodimethylamine and fed with curcumin-supplemented diet. The effect of curcumin-supplemented diet on histopathological changes and survival were assessed in relation to NF-κB activation, and the expression of NF-κB-related gene products involved in inflammation, DNA damage, apoptosis, cell proliferation, angiogenesis and metastasis. Our results showed that dietary administration of this nutraceutical significantly reduced the incidence of CCA and increased the survival of animals. This correlated with the suppression of the activation of transcription factors including NF-κB, AP-1 and STAT-3, and reduction in the expression of proinflammatory proteins such as COX-2 and iNOS. The formation of iNOS-dependent DNA lesions (8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine) was inhibited. Curcumin suppressed the expression of proteins related to cell survival (bcl-2 and bcl-xL), proliferation (cyclin D1 and c-myc), tumor invasion (MMP-9 and ICAM-1) and angiogenesis (VEGF), and microvessel density. Induction of apoptotic events as indicated by caspase activation and PARP cleavage was also noted. Our results suggest that curcumin exhibits an anticarcinogenic potential via suppression of various events involved in multiple steps of carcinogenesis, which is accounted for by its ability to suppress proinflammatory pathways.
胆管癌（CCA）是一种高度转移性肿瘤，与肝吸虫感染和摄入亚硝胺污染的食物有关，是东南亚地区的一个主要健康问题。为了寻找合适的化学预防剂，我们通过感染肝吸虫（Opisthorchis viverrini）并给予 N-亚硝二甲胺以及喂食富含姜黄素的饮食，在动物模型中研究了姜黄素（一种源自姜黄的传统抗炎剂）对 CCA 发展的影响。我们评估了富含姜黄素的饮食对 NF-κB 激活、涉及炎症、DNA 损伤、细胞凋亡、细胞增殖、血管生成和转移的 NF-κB 相关基因产物表达的组织病理学变化和生存的影响。我们的结果表明，这种营养保健品的饮食给药显著降低了 CCA 的发病率并提高了动物的存活率。这与转录因子 NF-κB、AP-1 和 STAT-3 的激活抑制以及促炎蛋白 COX-2 和 iNOS 的表达减少有关。抑制 iNOS 依赖性 DNA 损伤（8-硝基鸟嘌呤和 8-氧代-7,8-二氢-2'-脱氧鸟苷）的形成。姜黄素抑制与细胞存活（bcl-2 和 bcl-xL）、增殖（细胞周期蛋白 D1 和 c-myc）、肿瘤侵袭（MMP-9 和 ICAM-1）和血管生成（VEGF）相关的蛋白表达，以及微血管密度。还观察到诱导细胞凋亡事件，如 caspase 激活和 PARP 切割。我们的结果表明，姜黄素通过抑制致癌作用多个步骤中涉及的各种事件表现出抗癌潜力，这归因于其抑制促炎途径的能力。
