期刊
VIROLOGY JOURNAL
卷 14, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12985-017-0852-z
关键词
Recombinant Newcastle disease virus; Rabies virus glycoprotein; Lung adenocarcinoma; alpha 7 nicotinic acetylcholine receptors; Apoptosis
类别
资金
- Natural Science Foundation of Jiangsu Province [BK20151333]
- National Natural Science Foundation of China [81672999]
- Social Development Fund of Zhenjiang City, China [SH2013041]
Background: The aim of this study were to investigate the possible pro-apoptotic mechanisms of the recombinant Newcastle disease virus (NDV) strain rL-RVG, which expresses the rabies virus glycoprotein, in A549 lung adenocarcinoma cells via the regulation of alpha 7 nicotinic acetylcholine receptors (alpha 7 nAChRs) and to analyze the relationships between alpha 7 nAChR expression in lung cancer and the clinical pathological features. Methods: alpha 7 nAChR expression in A549, L.795, and small-cell lung carcinoma (SCLC) cells, among others, was detected using reverse transcription polymerase chain reaction (RT-PCR). The optimal alpha 7 nAChR antagonist and agonist concentrations for affecting A549 lung adenocarcinoma cells were detected using MTT assays. The alpha 7 nAChR expression in A549 cells after various treatments was assessed by Western blot, immunofluorescence and RT-PCR analyses. Apoptosis in the various groups was also monitored by Western blot and TUNEL assays, followed by the detection of cell migration via transwell and scratch tests. Furthermore, alpha 7 nAChR expression was examined by immunohistochemistry in lung cancer tissue samples from 130 patients and 40 pericancerous tissue samples, and the apoptotis in lung adenocarcinoma tissue was detected by Tunel assay, Then, the expression levels and clinicopathological characteristics were analyzed. Results: Of the A549, L.795, SCLC and U251 cell lines, the A549 cells exhibited the highest alpha 7 nAChR expression. The cells infected with rL-RVG exhibited high RVG gene and protein expression. The rL-RVG group exhibited weaker alpha 7 nAChR expression compared with the methyllycaconitine citrate hydrate (MLA, an alpha 7 nAChR antagonist) and NDV groups. At the same time, the MLA and rL-RVG treatments significantly inhibited proliferation and migration and promoted apoptosis in the lung cancer cells (P < 0.05). The expression of alpha 7 nAChR was upregulated in lung cancer tissue compared with pericancerous tissue (P = 0.000) and was significantly related to smoking, clinical tumor-node-metastases stage, and histological differentiation (P < 0.05). The AI in lung adenocarcinoma tissue in high-medium differentiation group was lower than that in low differentiation group (p < 0.01). Conclusions: An antagonist of alpha 7 nAChR may be used as a molecular target for lung adenocarcinoma therapy. Recombinant NDV rL-RVG enhances the apoptosis and inhibits the migration of A549 lung adenocarcinoma cells by regulating alpha 7 nAChR signaling pathways.
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