Protective effects of Celastrol on diethylnitrosamine-induced hepatocellular carcinoma in rats and its mechanisms
Protective effects of Celastrol on diethylnitrosamine-induced hepatocellular carcinoma in rats and its mechanisms
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DOI：
10.1016/j.ejphar.2016.04.045
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发表时间：
2016-08-05
影响因子：
5
通讯作者：
Wei, Wei
中科院分区：
文献类型：
--
作者：
Chang, Wei;He, Wei;Wei, Wei
雷公藤红素是雷公藤的活性成分，是一种传统中草药，因其潜在的抗炎和抗癌活性而引起人们的兴趣。本研究的目的是评估雷公藤红素对二乙基亚硝胺（DEN）诱导的大鼠肝细胞癌（HCC）的抗肿瘤作用，并进一步探讨其潜在机制。 Sprague-Dawley大鼠每周灌胃DEN（10 mg/kg）6天，持续16周。计算结节的数量。苏木精-伊红（HE）染色用于评估肝脏病理病变。采用Elisa试剂盒分析血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、甲胎蛋白(AFP)水平,以及p53、小鼠双分钟(MDM)2、Bax、Bcl-2、Bcl-xl、细胞色素C、Caspase-3、 通过蛋白质印迹分析 Caspase-9 和聚（ADP-核糖）聚合酶（PARP）。结果表明，与DEN治疗组相比，雷公藤红素组能显着降低死亡率、肿瘤结节数量和肝脏指数。此外，雷公藤红素可明显改善肝脏病理病变，降低升高的ALT、AST、ALP和AFP水平。同时，雷公藤红素抑制蛋白MDM2的表达，激活p53诱导的内在线粒体凋亡途径，抑制抗凋亡的Bcl-2和Bcl-xl，诱导促凋亡的Bax、细胞色素C、PARP和caspases。这些结果表明雷公藤红素对DEN诱导的HCC大鼠具有良好的治疗作用，这可能与雷公藤红素诱导肝癌细胞凋亡有关。 (C) 2016 Elsevier B.V. 保留所有权利。
Celastrol, an active ingredient of Tripterygium Wilfordii, is a traditional Chinese medicinal herb, which has attracted interests for its potential anti-inflammatory and anti-cancer activities. The aim of this study was to evaluate the anti-tumor effect of Celastrol against diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats and furthermore, to explore the underlying mechanism. Sprague-Dawley rats were intragastrically administered with DEN (10 mg/kg) for 6 days every week and persisting 16 weeks. The number of nodules was calculated. Hematoxylin-Eosin (HE) staining was used to evaluate the hepatic pathological lesions. The levels of serum alanine aminotransferase (ALT), glutamic oxalacetic transaminase (AST), alkaline phosphatase (ALP) and alpha fetoprotein (AFP) were analyzed by Elisa kits, and the protein levels of p53, Murine double minute (MDM) 2, Bax, Bcl-2, Bcl-xl, cytochrome C, Caspase-3, Caspase-9 and Poly (ADP-ribose) polymerase (PARP) were analyzed by western blot. The results showed that Celastrol could significantly decrease the mortality, the number of tumor nodules and the index of liver in the Celastrol groups compared with DEN-treated group. Moreover, Celastrol obviously improved the hepatic pathological lesions and decreased the elevated levels of ALT, AST, ALP and AFP. Meanwhile, Celastrol suppressed the expression of the protein MDM2, activated the intrinsic mitochondria) apoptosis pathway induced by p53, inhibited anti-apoptotic Bcl-2 and Bcl-xl, induced the pro-apoptotic Bax, cytochrome C, PARP and caspases. These results suggested that Celastrol had a good therapeutic action in reversing DEN-induced HCC rats, which may be associated with the apoptosis of hepatoma cells induced by Celastrol. (C) 2016 Elsevier B.V. All rights reserved.