Cancer Therapeutics and Chemoprevention Group, Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
Curr Pharm Biotechnol. 2012 Jan;13(1):229-34. doi: 10.2174/138920112798868575.
Hepatocellular carcinoma (HCC), one of the most common cancers in the world, is a leading cause of cancerrelated mortality. HCC develops most frequently in the background of oxidative stress and chronic hepatic inflammation due to viral infections, alcohol abuse as well as exposure to environmental and dietary carcinogens. As the prognosis of HCC is extremely poor and mostly unresponsive to current chemotherapeutic treatment regimens, novel preventive approaches like chemoprevention are urgently needed. We have recently found that resveratrol, a dietary polyphenol present in grapes, berries, peanuts as well as red wine, prevents diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats through suppression of inflammation and oxidative stress. As cytokines are considered to be important mediators of inflammation, the objective of the present study was to investigate the effects of resveratrol on hepatic cytokines during DENA-initiated hepatocarcinogenesis in rats. Liver samples were harvested from our previous study in which resveratrol (50, 100 and 300 mg/kg) was found to exert a chemopreventive action against rat liver tumorigenesis induced by DENA. The levels of proinflammatory cytokines, namely tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin- 6 (IL-6), were measured using enzyme-linked immunosorbent assays. The mRNA expression of these cytokines was studied by reverse transcriptase-polymerase chain reaction for comparison. Resveratrol treatment reversed the DENAinduced alteration of the level and expression of hepatic TNF-α, IL-1β and IL-6. From the current results in conjunction with our previous findings, it can be concluded that resveratrol-mediated chemoprevention of rat liver carcinogenesis is related to alteration of proinflammatory cytokines.
肝细胞癌 (HCC) 是世界上最常见的癌症之一，也是癌症相关死亡的主要原因。由于病毒感染、酗酒以及暴露于环境和饮食致癌物，HCC 通常在氧化应激和慢性肝炎症的背景下发展。由于 HCC 的预后极差，且对当前的化疗治疗方案大多没有反应，因此迫切需要新的预防方法，如化学预防。我们最近发现，白藜芦醇是一种存在于葡萄、浆果、花生和红酒中的膳食多酚，可通过抑制炎症和氧化应激来预防二乙基亚硝胺 (DENA) 诱导的大鼠肝癌发生。由于细胞因子被认为是炎症的重要介质，因此本研究的目的是研究白藜芦醇对 DENA 诱导的大鼠肝癌发生过程中肝细胞因子的影响。本研究使用酶联免疫吸附测定法检测了肝组织样品中的促炎细胞因子，如肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β) 和白细胞介素-6 (IL-6) 的水平。通过逆转录-聚合酶链反应研究这些细胞因子的 mRNA 表达情况，以便进行比较。白藜芦醇治疗可逆转 DENA 诱导的肝 TNF-α、IL-1β 和 IL-6 水平和表达的改变。从目前的结果以及我们之前的发现可以得出结论，白藜芦醇介导的大鼠肝癌化学预防与促炎细胞因子的改变有关。
