Suppression of the Inflammatory Cascade is Implicated in Resveratrol Chemoprevention of Experimental Hepatocarcinogenesis
Suppression of the Inflammatory Cascade is Implicated in Resveratrol Chemoprevention of Experimental Hepatocarcinogenesis
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DOI：
10.1007/s11095-010-0144-4
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发表时间：
2010-06-01
影响因子：
3.7
通讯作者：
Darvesh, Altaf S.
中科院分区：
文献类型：
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作者：
Bishayee, Anupam;Waghray, Abhijeet;Darvesh, Altaf S.
白藜芦醇，存在于葡萄和红葡萄酒中，已被发现可以防止二乙基亚硝胺（DENA）引发的大鼠肝脏肿瘤发生，尽管其化学预防机制尚未完全阐明。本研究旨在探讨白藜芦醇的抗肝癌作用是否与白藜芦醇的抗肿瘤特性有关。肝组织样本来自20周的化学预防研究，其中白藜芦醇（50，100和300 mg/kg）以剂量反应方式抑制DENA诱导的Sprague-Dawley大鼠肝细胞结节。采用免疫组化和Western blot技术研究了肝肿瘤前和炎症标志物，即热休克蛋白（HSP 70）、环氧合酶-2（考克斯-2）和核因子-κ B（NF-κ B）。白藜芦醇还减弱了DENA介导的NF-κ B p65从细胞质到细胞核的易位，并稳定抑制性κ B。目前的研究结果表明，白藜芦醇可能通过抑制升高的HSP 70，考克斯-2以及NF-κ B水平，从而在DENA诱发的大鼠肝癌发生过程中发挥化学预防作用。这些有益的作用与良好的安全性相结合，鼓励白藜芦醇用于人类HCC的化学预防和干预的发展，这仍然是一种毁灭性的疾病。
Resveratrol, present in grapes and red wine, has been found to prevent diethylnitrosamine (DENA)-initiated rat liver tumorigenesis, though the chemopreventive mechanisms are not completely elucidated. The current study was designed to explore whether the antiinflammatory properties of resveratrol play a role in its antihepatocarcinogenic action.Liver samples were harvested from a 20-week chemopreventive study in which resveratrol (50, 100 and 300 mg/kg) was shown to inhibit DENA-induced hepatocyte nodules in Sprague-Dawley rats in a dose-responsive manner. Hepatic preneoplastic and inflammatory markers, namely heat shock protein (HSP70), cyclooxygenase-2 (COX-2) and nuclear factor-kappa B (NF-kappa B), were studied using immunohistochemical as well as Western blot techniques.Resveratrol dose-dependently suppressed DENA-induced increased expressions of hepatic HSP70 and COX-2. Resveratrol also attenuated the DENA-mediated translocation of NF-kappa B p65 from the cytosol to the nucleus with stabilization of inhibitory kappa B.The present findings indicate that resveratrol exerts chemoprevention of hepatocarcinogenesis possibly through antiinflammatory effects during DENA-evoked rat liver carcinogenesis by suppressing elevated levels of HSP70, COX-2 as well as NF-kappa B. These beneficial effects combined with an excellent safety profile encourage the development of resveratrol for chemoprevention and intervention of human HCC that remains a devastating disease.