Comparison of the regulation of β-catenin signaling by type I, type II and type III interferons in hepatocellular carcinoma cells

• Published in: PloS one 2012-10, Vol.7 (10), p.e47040
• Main Authors: Li, Wei, Huang, Xiaojie, Tong, Hongfei, Wang, Yuxuan, Zhang, Tong, Wang, Wen, Dai, Lili, Li, Tongzeng, Lin, Shengzhang, Wu, Hao
• Format: Article
• Language: English
• Subjects: Activation; Anticancer properties; Apoptosis; Apoptosis - drug effects; beta Catenin - genetics; beta Catenin - metabolism; Biological effects; Biology; Carcinogenesis; Carcinogens; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Cytokines; Cytometry; Dkk1 protein; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Hep G2 Cells; Hepatocellular carcinoma; Humans; In Situ Nick-End Labeling; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Interferon; Interferon Type I - pharmacology; Interferon-gamma - pharmacology; Interferons - pharmacology; Kinases; Liver cancer; Medicine; Pathways; Rodents; Signal transduction; Signal Transduction - drug effects; Signal Transduction - genetics; Signaling; Stat1 protein; STAT1 Transcription Factor - genetics; STAT1 Transcription Factor - metabolism; Stat3 protein; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Tumor cell lines; β-Catenin; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0047040

IFNs are a group of cytokines that possess potent antiviral and antitumor activities, while β-catenin pathway is a proliferative pathway involved in carcinogenesis. Interaction between these two pathways has not been well elaborated in hepatocellular carcinoma (HCC). HCC cell lines, HepG2 and Huh7, were used in this study. β-catenin protein levels and corresponding signaling activities were observed by flow cytometry and luciferase assay, respectively. Cell proliferation was quantified by counting viable cells under microscope, and apoptosis by TUNEL assay. DKK1 and GSK3β levels were determined by flow cytometry. Secreted DKK1 was tested by ELISA. FLUD, S3I and aDKK1 were used to inhibit STAT1, STAT3 and DKK1 activities, respectively. Our findings show that all three types of IFNs, IFNα, IFNγ and IFNλ, are capable of inhibiting β-catenin signaling activity in HepG2 and Huh7 cells, where IFNγ was the strongest (p