EGFR may participate in immune evasion through regulation of B7‑H5 expression in non‑small cell lung carcinoma

Dong,Zhaohui; Zhang,Lanying; Xu,Wei; Zhang,Gensheng

doi:10.3892/mmr.2018.9361

EGFR may participate in immune evasion through regulation of B7‑H5 expression in non‑small cell lung carcinoma

Authors:
- Zhaohui Dong
- Lanying Zhang
- Wei Xu
- Gensheng Zhang
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Affiliations: Intensive Care Unit, The First People's Hospital of Huzhou, Huzhou, Zhejiang 313000, P.R. China, Intensive Care Unit, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
Published online on: August 8, 2018 https://doi.org/10.3892/mmr.2018.9361
Pages: 3769-3779
Copyright: © Dong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lung cancer is one of the most prevalent malignancies worldwide; it has been ranked the most lethal type of cancer. Non‑small cell lung carcinoma (NSCLC) comprises >80% of all types of lung cancer. Although certain achievements have been made in the treatment of NSCLC, including the targeted gene drug epidermal growth factor receptor‑tyrosine kinase inhibitor (EGFR‑TKI), the five‑year survival rate of patients has not significantly increased. A previous study demonstrated that B7‑H5, a novel co‑stimulatory molecule in the B7 molecule family, was negatively correlated with EGFR in pancreatic cancer. Thus, in the present study, we aimed to investigate whether EGFR participates in immune evasion, probably through regulation of B7‑H5 expression. NCI‑H1299 NSCLCL cells were divided into control, mock, small interfering‑EGFR and EGFR‑TKI groups. The cell viability and apoptosis rate were analysed by a Cell Counting Kit‑8 assay and flow cytometry. The transforming growth factor (TGF)‑β and interleukin (IL)‑10 content was measured using an ELISA. The expression levels of EGFR, B7‑H5, Survivin, apoptosis regulator Bax, apoptosis regulator Bcl‑2 (Bcl‑2), TGF‑β, vascular endothelial growth factor (VEGF), IL‑10 and cyclooxygenase (COX)‑2 were assessed via quantitative PCR and western blotting. The activation of the tyrosine‑protein kinase JAK2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signalling pathway was detected using western blotting. The results demonstrated a notable negative correlation between EGFR and B7‑H5 expression levels in cancer tissues and cell lines. Inhibition of EGFR expression via gene silencing and EGFR inhibition markedly decreased cell viability and increased the apoptosis of NCI‑H1299 cells, by upregulating survivin and Bcl‑2 expression. The protein expression levels of TGF‑β, VEGF, IL‑10 and COX‑2 were additionally decreased, with weak activation of the JAK2/STAT3 signalling pathway. EGFR may be involved in immune evasion, possibly through regulation of B7‑H5 expression in NSCLC.

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