TY - JOUR
T1 - Interferon-alpha enhances the antitumour activity of EGFR-targeted therapies by upregulating RIG-I in head and neck squamous cell carcinoma
AU - Ma, Hailong
AU - Jin, Shufang
AU - Yang, Wenyi
AU - Zhou, Ge
AU - Zhao, Mei
AU - Fang, Sijie
AU - Zhang, Zhiyuan
AU - Hu, Jingzhou
N1 - Publisher Copyright:
© The Author(s) named above 2018.
PY - 2018/2/20
Y1 - 2018/2/20
N2 - Background:The epidermal growth factor receptor (EGFR)-targeted therapies have been tested in the clinic as treatments for head and neck squamous cell carcinoma (HNSCC). Owing to intrinsic or acquired resistance, EGFR-targeted therapies often lead to a low response rate and treatment failure. Interferon-alpha (IFNα) is a chemosensitising agent and multi-functional cytokine with a tumour inhibitory effect. However, the synergic effect of IFNα and EGFR-targeted therapies (erlotinib and nimotuzumab) and their mechanisms in HNSCC remain unclear.Methods:The interactions between IFNα, erlotinib, and nimotuzumab were evaluated in vitro in HNSCC cells. The synergistic effect of IFNα (20 000 IU per day, s.c.), erlotinib (50 mg kg -1 per day, i.g.) and nimotuzumab (10 mg kg -1 per day, i.p.) was further confirmed in vivo using HNSCC xenografts in nude mice. The upregulation of retinoic-acid inducible gene I (RIG-I) induced by IFNα and EGFR-targeted therapies and its mechanism were detected in vitro and in vivo.Results:IFNα enhances the antitumour effects of erlotinib and nimotuzumab on HNSCC cells both in vitro and in vivo. Importantly, both IFNα and EGFR-targeted therapies promote the expression of RIG-I by activating signal transducers and activators of transcription 1 (STAT1) in HNSCC cells. RIG-I knockdown reduced the sensitivity of HN4 and HN30 cells to IFNα, erlotinib, and nimotuzumab. Moreover, IFNα transcriptionally induced RIG-I expression in HNSCC cells through STAT1.Conclusions:IFNα enhances the effect of EGFR-targeted therapies by upregulating RIG-I, and its expression may represent a predictor of the effectiveness of a combination treatment including IFNα in HNSCC.
AB - Background:The epidermal growth factor receptor (EGFR)-targeted therapies have been tested in the clinic as treatments for head and neck squamous cell carcinoma (HNSCC). Owing to intrinsic or acquired resistance, EGFR-targeted therapies often lead to a low response rate and treatment failure. Interferon-alpha (IFNα) is a chemosensitising agent and multi-functional cytokine with a tumour inhibitory effect. However, the synergic effect of IFNα and EGFR-targeted therapies (erlotinib and nimotuzumab) and their mechanisms in HNSCC remain unclear.Methods:The interactions between IFNα, erlotinib, and nimotuzumab were evaluated in vitro in HNSCC cells. The synergistic effect of IFNα (20 000 IU per day, s.c.), erlotinib (50 mg kg -1 per day, i.g.) and nimotuzumab (10 mg kg -1 per day, i.p.) was further confirmed in vivo using HNSCC xenografts in nude mice. The upregulation of retinoic-acid inducible gene I (RIG-I) induced by IFNα and EGFR-targeted therapies and its mechanism were detected in vitro and in vivo.Results:IFNα enhances the antitumour effects of erlotinib and nimotuzumab on HNSCC cells both in vitro and in vivo. Importantly, both IFNα and EGFR-targeted therapies promote the expression of RIG-I by activating signal transducers and activators of transcription 1 (STAT1) in HNSCC cells. RIG-I knockdown reduced the sensitivity of HN4 and HN30 cells to IFNα, erlotinib, and nimotuzumab. Moreover, IFNα transcriptionally induced RIG-I expression in HNSCC cells through STAT1.Conclusions:IFNα enhances the effect of EGFR-targeted therapies by upregulating RIG-I, and its expression may represent a predictor of the effectiveness of a combination treatment including IFNα in HNSCC.
UR - http://www.scopus.com/inward/record.url?scp=85042362100&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042362100&partnerID=8YFLogxK
U2 - 10.1038/bjc.2017.442
DO - 10.1038/bjc.2017.442
M3 - Article
C2 - 29348488
AN - SCOPUS:85042362100
SN - 0007-0920
VL - 118
SP - 509
EP - 521
JO - British journal of cancer
JF - British journal of cancer
IS - 4
ER -