雷帕霉素靶蛋白（mTOR）抑制剂雷帕霉素类似物（rapalog）LEGALON-SIL 可下调人源全长 HCV 表达的人肝细胞中的 HCV 核心蛋白和 NS5A。
Legalon-SIL downregulates HCV core and NS5A in human hepatocytes expressing full-length HCV.
机构信息
The Liver-Biliary-Pancreatic Center, Cannon Research Center, Carolinas Medical Center, Charlotte, NC 28203, United States.
出版信息
World J Gastroenterol. 2011 Apr 7;17(13):1694-700. doi: 10.3748/wjg.v17.i13.1694.
AIM
To determine the effect of Legalon-SIL (LS) on hepatitis C virus (HCV) core and NS5A expression and on heme oxygenase-1 (HMOX-1) and its transcriptional regulators in human hepatoma cells expressing full length HCV genotype 1b.
METHODS
CON1 cells were treated with 50 μmol/L or 200 μmol/L LS. Cells were harvested after 2, 6 and 24 h. HCV RNA and protein levels were determined by quantitative real-time polymerase chain reaction and Western blotting, respectively.
RESULTS
HCV RNA (core and NS5A regions) was decreased after 6 h with LS 200 μmol/L (P < 0.05). Both 50 and 200 μmol/L LS decreased HCV RNA levels [core region (by 55% and 88%, respectively) and NS5A region (by 62% and 87%, respectively) after 24 h compared with vehicle (dimethyl sulphoxide) control (P < 0.01). Similarly HCV core and NS5A protein were decreased (by 85%, P < 0.01 and by 65%, P < 0.05, respectively) by LS 200 μmol/L. Bach1 and HMOX-1 RNA were also downregulated by LS treatment (P < 0.01), while Nrf2 protein was increased (P < 0.05).
CONCLUSION
Our results demonstrate that treatment with LS downregulates HCV core and NS5A expression in CON1 cells which express full length HCV genotype 1b, and suggests that LS may prove to be a valuable alternative or adjunctive therapy for the treatment of HCV infection.
目的
确定 Legalon-SIL（LS）对表达全长丙型肝炎病毒（HCV）基因型 1b 的人肝癌细胞中 HCV 核心和 NS5A 表达以及血红素加氧酶-1（HMOX-1）及其转录调节剂的影响。
方法
用 50 μmol/L 或 200 μmol/L LS 处理 CON1 细胞。分别在 2、6 和 24 h 后收获细胞。通过实时定量聚合酶链反应和 Western blot 测定 HCV RNA 和蛋白质水平。
结果
LS 200 μmol/L 处理 6 h 后 HCV RNA（核心和 NS5A 区）降低（P < 0.05）。50 和 200 μmol/L LS 均降低 HCV RNA 水平[核心区（分别降低 55%和 88%）和 NS5A 区（分别降低 62%和 87%），与 DMSO 对照组相比（P < 0.01）。同样，LS 200 μmol/L 还降低了 HCV 核心和 NS5A 蛋白（分别降低 85%，P < 0.01 和 65%，P < 0.05）。LS 处理还下调 Bach1 和 HMOX-1 RNA（P < 0.01），而 Nrf2 蛋白增加（P < 0.05）。
结论
我们的结果表明，LS 处理下调了表达全长 HCV 基因型 1b 的 CON1 细胞中 HCV 核心和 NS5A 的表达，表明 LS 可能成为治疗 HCV 感染的有价值的替代或辅助治疗方法。
Zotero 插件