Potential anti-tumor effect of IFN-λ2 (IL-28A) against human lung cancer cells

被引：53

作者：

Tezuka, Yasuhiro ^{[1
,2
,3
]}

Endo, Shunsuke ^{[2
]}

Matsui, Aya ^{[1
,3
]}

Sato, Atsuko ^{[4
]}

Saito, Katsuyo ^{[1
]}

Semba, Kentaro ^{[5
]}

Takahashi, Masafumi ^{[3
]}

Murakami, Takashi ^{[1
]}

机构：

[1] Takasaki Univ Hlth & Welf, Fac Pharm, Lab Tumor Biol, Takasaki, Gunma 3700033, Japan

[2] Jichi Med Univ, Dept Gen Thorac Surg, Shimotsuke, Tochigi 3290498, Japan

[3] Jichi Med Univ, Ctr Mol Med, Div Bioimaging Sci, Shimotsuke, Tochigi 3290498, Japan

[4] Jichi Med Univ, Dept Dermatol, Shimotsuke, Tochigi 3290498, Japan

[5] Waseda Univ, Dept Life Sci & Med Biosci, Shinjuku Ku, Tokyo 1628480, Japan

来源：

LUNG CANCER | 2012年 / 78卷 / 03期

关键词：

Type III interferon; IL-28A; Non-small cell lung cancer; EGFR mutation; Apoptosis; Bioluminescent imaging; INTERFERON-LAMBDA; TARGETED THERAPIES; III INTERFERON; MELANOMA-CELLS; I INTERFERON; TUMOR; RECEPTOR; MAINTENANCE; CARCINOMA; MIGRATION;

D O I：

10.1016/j.lungcan.2012.09.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Interferon (IFN)-lambda s (IL-28A/IL-28B/IL-29) classified as type III IFNs, are the latest members identified of the interferon family. As with type I IFNs such as IFN-alpha, type III IFNs share antiviral and antitumor activity and may have fewer side effects due to a more selective receptor distribution. Therefore, type III IFNs may be clinically useful for human viral and malignant diseases. Here we demonstrate the potential anti-tumor effect of IFN-lambda 2 (IL-28A) against human lung cancer cells. All lung cancer cell lines that we examined expressed both IFN-lambda receptors (IL-28R1 and IL-10R2). Lung cancer cells with epidermal growth factor receptor (EGFR) mutations were more sensitive to IFN-lambda 2 treatment compared with cells with KRAS mutations. HCC827 cells with an EGFR mutation treated with IFN-lambda 2 underwent growth suppression and apoptotic cell death by STAT1 phosphorylation. Administration of neutralizing antibodies to IFN-lambda inhibited caspase-3/7 activity induced by IFN-lambda 2. Finally, in vivo luminescent imaging also demonstrated the anti-tumor effect of IFN-lambda 2 in a cancer cell transplant animal model. Taken together, IFN-lambda 2 would be a new therapeutic agent for clinical lung cancers with EGFR mutations. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

引用

页码：185 / 192

页数：8

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