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Suppression of hepatocellular carcinoma proliferation and hepatitis B surface antigen secretion with interferon‐λ1 or PEG‐interferon‐λ1
Author(s) -
Tian Shuo,
Hui Xiwu,
Fan Zhenzhen,
Li Qinshan,
Zhang Junwen,
Yang Xia,
Ma Xiaoli,
Huang Bingren,
Chen Deng,
Chen Hong
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.14-250704
Subject(s) - hbsag , hepatocellular carcinoma , hepatitis b virus , interferon , in vivo , medicine , cancer research , cell growth , apoptosis , immunology , cytokine , virus , biology , biochemistry , genetics , microbiology and biotechnology
Hepatocellular carcinoma (HCC) is a common cancer associated with chronic hepatitis B virus (HBV) infection. Conventional interferon‐α (IFN‐α) and pegylated IFNs (PEG‐IFNs) approved for chronic HBV infection treatment can reduce the risk of HCC but are not suitable for the majority of patients and cause significant side effects. IFN‐λ1 is a type III IFN with antiviral, antiproliferative, and immunomodulatory functions similar to type I IFNs but with fewer side effects. However, the tolerability and antitumor activity of PEG‐IFN‐λ1 in HCC xenograft mice are unknown. In vitro IFN‐λ1 treatment of Hep3B and Huh7 human hepatoma cell lines increased MHC class I expression, activated JAK‐STAT signaling pathways, induced IFN‐stimulated gene expression, and inhibited hepatitis B surface antigen (HBsAg) expression. IFN‐λ1 treatment also caused 23.2 and 19.9% growth inhibition of Hep3B and Huh7 cells, respectively, and promoted cellular apoptosis. PEG‐IFN‐λ1, but not IFN‐λ1 treatment, significantly suppressed tumor growth (P = 0.002) and induced tumor cell apoptosis in a Hep3B cell xenograft mouse model without significant weight loss or toxicity. PEG‐IFN‐λ1 also significantly inhibited (P = 0.000) serum HBsAg secretion from Hep3B xenograft tumors in vivo. Thus, PEG‐IFN‐λ1 can suppress Hep3B xenograft tumor growth and inhibit HBsAg production and may be a potential treatment for HBV‐related HCC.—Tian, S., Hui, X., Fan, Z., Li, Q., Zhang, J., Yang, X., Ma, X., Huang, B., Chen, D., Chen, H. Suppression of hepatocellular carcinoma proliferation and hepatitis B surface antigen secretion with interferon‐λ1 or PEG‐interferon‐λ1. FASEB J. 28, 3528–3539 (2014). www.fasebj.org