Xu Bingfa, Tang Bo, Wei Jiajia
Department of Pharmacy, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, P.R. China.
Department of Pharmacy, Huainan First People's Hospital, Huainan, Anhui 232007, P.R. China.
Exp Ther Med. 2021 Jun;21(6):550. doi: 10.3892/etm.2021.9982. Epub 2021 Mar 24.
The objective of the present study was to explore the mechanism of hepatitis B virus (HBV) resistance to interferon (IFN), and the role of signal transducer and activator of transcription 1 (STAT1). HepG2.2.15 cells were stimulated with a long-term (6-24 weeks) low-dose interferon (IFN)α-2b (10-70 IU/ml), so as to construct and screen a HepG2.2.15 cell model resistant to IFNα-2b. The changes of STAT1 and other proteins in the JAK-STAT signaling pathway, before and after drug resistance, were compared. The phosphorylation of STAT1 in HepG2.2.15 cells resistant to IFNα-2b was significantly decreased, and the expression level of 2',5'-oligoadenylate synthetase 1 was downregulated. Decreased phosphorylation of STAT1 in the JAK-STAT signaling pathway a contributor to the development of resistance to IFN-α in HBV.
本研究的目的是探讨乙型肝炎病毒（HBV）对干扰素（IFN）耐药的机制，以及信号转导和转录激活因子1（STAT1）的作用。用长期（6 - 24周）低剂量干扰素（IFN）α-2b（10 - 70 IU/ml）刺激HepG2.2.15细胞，以构建和筛选对IFNα-2b耐药的HepG2.2.15细胞模型。比较耐药前后JAK-STAT信号通路中STAT1和其他蛋白质的变化。对IFNα-2b耐药的HepG2.2.15细胞中STAT1的磷酸化显著降低，2',5'-寡腺苷酸合成酶1的表达水平下调。JAK-STAT信号通路中STAT1磷酸化降低是HBV对IFN-α耐药产生的一个因素。
