Zheng Liyun, Wang Qiang, Yang Xiaorui, Guo Xiaohe, Chen Lu, Tao Le, Dong Lihong, Li Yujiang, An Haoyun, Yu Xuejun, Wang Qingduan, Chang Junbiao
Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, PR China.
Antivir Ther. 2012;17(4):679-87. doi: 10.3851/IMP2094. Epub 2012 Mar 27.
New drugs are needed to combat HBV infection. We investigated the anti-HBV activity of the deoxycytidine analogue FNC, which has anticancer activity and has been found to inhibit HCV replication.
In this study, a human hepatoma HepG2.2.15 cell culture system and duck HBV (DHBV) infection model were used as the in vitro and in vivo models to evaluate the anti-HBV activity of FNC.
In the cell model, FNC effectively suppressed the secretion of the HBV antigens in a dose-dependent manner, with 50% effective concentration values of 0.037 μM for hepatitis B surface antigen and 0.044 μM for hepatitis B e antigen on day 9. Consistent with the HBV antigen reduction, FNC also reduced the HBV DNA level by 92.31% and 93.90% intracellularly and extracellularly, respectively. DHBV DNA levels were markedly reduced after treatment with the FNC at 0.5, 1.0 and 2.0 mg/kg•day dosages. The inhibition rate of FNC at the dose of 2.0 mg/kg•day reached 91.68% and 81.96%, in duck serum and liver, respectively, on day 10. Furthermore, significant liver histology restoration after FNC treatment was observed, as evaluated by the histopathological analysis.
FNC can evidently inhibit the replication of HBV in the HepG2.2.15 cell line in vitro and inhibits DHBV replication in ducks in vivo. It could be potentially developed into a new anti-HBV drug.
对抗乙型肝炎病毒（HBV）感染需要新型药物。我们研究了脱氧胞苷类似物FNC的抗HBV活性，该类似物具有抗癌活性，且已发现其可抑制丙型肝炎病毒（HCV）复制。
在本研究中，使用人肝癌HepG2.2.15细胞培养系统和鸭乙型肝炎病毒（DHBV）感染模型作为体外和体内模型，以评估FNC的抗HBV活性。
在细胞模型中，FNC以剂量依赖性方式有效抑制HBV抗原的分泌，在第9天，乙型肝炎表面抗原的50%有效浓度值为0.037μM，乙型肝炎e抗原的50%有效浓度值为0.044μM。与HBV抗原减少一致，FNC在细胞内和细胞外分别使HBV DNA水平降低了92.31%和93.90%。用0.5、1.0和2.0mg/kg•天剂量的FNC处理后，DHBV DNA水平显著降低。在第10天，2.0mg/kg•天剂量的FNC在鸭血清和肝脏中的抑制率分别达到91.68%和81.96%。此外，通过组织病理学分析评估，观察到FNC治疗后肝脏组织学有明显恢复。
FNC在体外可明显抑制HBV在HepG2.2.15细胞系中的复制，并在体内抑制鸭体内的DHBV复制。它有可能被开发成为一种新型抗HBV药物。
