Interferon-alpha enhances the antitumour activity of EGFR-targeted therapies by upregulating RIG-I in head and neck squamous cell carcinoma.
Interferon-alpha enhances the antitumour activity of EGFR-targeted therapies by upregulating RIG-I in head and neck squamous cell carcinoma.
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干扰素-α 通过上调头颈鳞状细胞癌中的 RIG-I 增强 EGFR 靶向治疗的抗肿瘤活性
DOI：
10.1038/bjc.2017.442
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发表时间：
2018-02-20
影响因子：
8.8
通讯作者：
Hu J
中科院分区：
文献类型：
--
作者：
Ma H;Jin S;Yang W;Zhou G;Zhao M;Fang S;Zhang Z;Hu J
背景：表皮生长因子受体（EGFR）靶向治疗已经在临床上用于头颈部鳞状细胞癌（HNSCC）的治疗。由于内在或获得性耐药，EGFR靶向治疗通常导致低应答率和治疗失败。干扰素-α（IFNα）是一种具有肿瘤抑制作用的化学增敏剂和多功能细胞因子。然而，IFNα和EGFR靶向治疗（厄洛替尼和尼妥珠单抗）的协同作用及其在HNSCC.Methods中的机制尚不清楚：IFNα，厄洛替尼和尼妥珠单抗之间的相互作用在体外HNSCC细胞中进行了评估。使用裸小鼠HNSCC异种移植物在体内进一步证实了IFNα（20 000 IU/天，皮下）、厄洛替尼（50 mg kg-1/天，IG）和尼妥珠单抗（10 mg kg-1/天，ip）的协同作用。结果：IFNα能增强厄洛替尼和尼妥珠单抗对HNSCC细胞的体内、外抗肿瘤作用。重要的是，IFNα和EGFR靶向治疗均通过激活HNSCC细胞中的信号转导和转录激活因子1（STAT 1）促进RIG-I的表达。RIG-I敲低降低了HN 4和HN 30细胞对IFNα、厄洛替尼和尼妥珠单抗的敏感性。结论：IFNα通过上调RIG-I的表达增强EGFR靶向治疗的疗效，其表达可作为联合治疗HNSCC疗效的预测指标。
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, sc), erlotinib (50 mg kg− 1 per day, ig) and nimotuzumab (10 mg kg− 1 per day, ip) 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.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
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DOI：
10.1186/s13046-017-0575-4
发表时间：
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期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
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DOI：
10.1084/jem.20131556
发表时间：
2014-05-05
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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