Dual effects of the Nrf2 inhibitor for inhibition of hepatitis C virus and hepatic cancer cells.
Dual effects of the Nrf2 inhibitor for inhibition of hepatitis C virus and hepatic cancer cells.
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DOI：
10.1186/s12885-018-4588-y
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发表时间：
2018-06-25
期刊：
影响因子：
3.8
通讯作者：
Saito H
中科院分区：
文献类型：
--
作者：
Murakami Y;Sugiyama K;Ebinuma H;Nakamoto N;Ojiro K;Chu PS;Taniki N;Saito Y;Teratani T;Koda Y;Suzuki T;Saito K;Fukasawa M;Ikeda M;Kato N;Kanai T;Saito H
我们先前的研究表明，抑制核因子E2相关因子2(NRF2)可以抑制丙型肝炎病毒(HCV)的感染。本研究探讨了Nrf2抑制剂Brusatol是否具有抗丙型肝炎病毒和抗癌的双重作用。通过分析持续感染丙型肝炎病毒的肝细胞系HPI细胞中的丙型肝炎病毒RNA和蛋白，以及通过分析复制复制子复制的肝细胞系OR6细胞中的丙型肝炎病毒复制，研究了灯盏花醇的抗丙型肝炎病毒作用。然后，研究了灯盏花醇的双重抗丙型肝炎病毒和抗癌作用，以及灯盏花醇与已报道具有双重作用的抗癌药物索拉非尼联合使用时的增强作用。布鲁塞尔醇在RNA和蛋白质水平上抑制了持续的丙型肝炎病毒感染，并与HPI细胞中Nrf2蛋白的减少有关。对用鸦胆子醇处理的OR6细胞的分析表明，鸦胆子醇通过抑制丙型肝炎病毒的复制来抑制丙型肝炎病毒的持久性。Brusatol与抗癌药物联用不仅增强了抗癌作用，而且在与索拉非尼联用的情况下，还强烈抑制了丙型肝炎病毒的感染。布鲁塞尔醇具有抗丙型肝炎病毒和抗癌的双重作用，可以增强索拉非尼的类似作用。因此，Brusatol和索拉非尼联合治疗丙型肝炎病毒相关性肝细胞癌是有可能的。本文的在线版本(10.1186/s12885-0184588-y)包含向授权用户提供的补充材料。
We previously showed that knockdown of nuclear factor E2-related factor 2 (Nrf2) resulted in suppression of hepatitis C virus (HCV) infection. In this study, whether brusatol, an Nrf2 inhibitor, has dual anti-HCV and anticancer effects was explored. The anti-HCV effect of brusatol was investigated by analyzing HCV RNA and proteins in a hepatic cell line persistently-infected with HCV, HPI cells, and by analyzing HCV replication in a replicon-replicating hepatic cell line, OR6 cells. Then, dual anti-HCV and anticancer effects of brusatol and enhancement of the effects by the combination of brusatol with anticancer drugs including sorafenib, which has been reported to have the dual effects, were then investigated. Brusatol suppressed the persistent HCV infection at both the RNA and protein levels in association with a reduction in Nrf2 protein in the HPI cells. Analysis of the OR6 cells treated with brusatol indicated that brusatol inhibited HCV persistence by inhibiting HCV replication. Combination of brusatol with an anticancer drug not only enhanced the anticancer effect but also, in the case of the combination with sorafenib, strongly suppressed HCV infection. Brusatol has dual anti-HCV and anticancer effects and can enhance the comparable effects of sorafenib. There is therefore the potential for combination therapy of brusatol and sorafenib for HCV-related hepatocellular carcinoma. The online version of this article (10.1186/s12885-018-4588-y) contains supplementary material, which is available to authorized users.
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