Cargando…

High-dose irradiation in combination with toll-like receptor 9 agonist CpG oligodeoxynucleotide 7909 downregulates PD-L1 expression via the NF-κB signaling pathway in non-small cell lung cancer cells

OBJECTIVES: Irradiation resistance appears as local recurrence and distant metastasis in advanced stages of non-small cell lung cancer (NSCLC). High-dose irradiation combined with immunotherapy improved overall survival and local control of NSCLC. This study explored the underlying molecular mechani...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Xue, Zhang, Qi, Luo, Youjun, Gao, Caixia, Zhuang, Xibing, Xu, Guoxiong, Qiao, Tiankui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085295/
https://www.ncbi.nlm.nih.gov/pubmed/27799798
http://dx.doi.org/10.2147/OTT.S116629
_version_ 1782463545638649856
author Chen, Xue
Zhang, Qi
Luo, Youjun
Gao, Caixia
Zhuang, Xibing
Xu, Guoxiong
Qiao, Tiankui
author_facet Chen, Xue
Zhang, Qi
Luo, Youjun
Gao, Caixia
Zhuang, Xibing
Xu, Guoxiong
Qiao, Tiankui
author_sort Chen, Xue
collection PubMed
description OBJECTIVES: Irradiation resistance appears as local recurrence and distant metastasis in advanced stages of non-small cell lung cancer (NSCLC). High-dose irradiation combined with immunotherapy improved overall survival and local control of NSCLC. This study explored the underlying molecular mechanism by which the effect of high-dose irradiation plus toll-like receptor 9 (TLR9) agonist CpG oligodeoxynucleotide (CpG ODN) 7909 on NSCLC. MATERIALS AND METHODS: NSCLC H460 cells were exposed to constant high-dose irradiation (6.37 Gy) in irradiation (IR) group and the irradiation plus CpG group. Gene expression was assessed using quantitative reverse transcriptase-polymerase chain reaction and Western blot. Knockdown of nuclear factor kappa B (NF-κB) p65 expression was conducted using p65 siRNA. RESULTS: Expression of programmed death-ligand 1 (PD-L1) mRNA was significantly decreased in IR combined with CpG ODN 7909 group compared with the control or IR-alone groups (P<0.05). TLR9 expression was also obviously increased in the combination group compared with the control (P<0.05). Moreover, expression of NF-κB p65 was apparently reduced in the combination group compared with the control (P<0.05). However, expression of PD-L1 was significantly decreased after knockdown of p65 in IR group (P<0.05), but increased in the combination group (P<0.05) and slightly increased in CpG ODN-alone group (P<0.05), which was opposite to that without p65 knockdown group. CONCLUSION: This study demonstrated that radiotherapy combined with CpG ODN 7909 was able to downregulate PD-L1 expression through inhibition via the NF-κB signaling pathway.
format Online
Article
Text
id pubmed-5085295
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Dove Medical Press
record_format MEDLINE/PubMed
spelling pubmed-50852952016-10-31 High-dose irradiation in combination with toll-like receptor 9 agonist CpG oligodeoxynucleotide 7909 downregulates PD-L1 expression via the NF-κB signaling pathway in non-small cell lung cancer cells Chen, Xue Zhang, Qi Luo, Youjun Gao, Caixia Zhuang, Xibing Xu, Guoxiong Qiao, Tiankui Onco Targets Ther Original Research OBJECTIVES: Irradiation resistance appears as local recurrence and distant metastasis in advanced stages of non-small cell lung cancer (NSCLC). High-dose irradiation combined with immunotherapy improved overall survival and local control of NSCLC. This study explored the underlying molecular mechanism by which the effect of high-dose irradiation plus toll-like receptor 9 (TLR9) agonist CpG oligodeoxynucleotide (CpG ODN) 7909 on NSCLC. MATERIALS AND METHODS: NSCLC H460 cells were exposed to constant high-dose irradiation (6.37 Gy) in irradiation (IR) group and the irradiation plus CpG group. Gene expression was assessed using quantitative reverse transcriptase-polymerase chain reaction and Western blot. Knockdown of nuclear factor kappa B (NF-κB) p65 expression was conducted using p65 siRNA. RESULTS: Expression of programmed death-ligand 1 (PD-L1) mRNA was significantly decreased in IR combined with CpG ODN 7909 group compared with the control or IR-alone groups (P<0.05). TLR9 expression was also obviously increased in the combination group compared with the control (P<0.05). Moreover, expression of NF-κB p65 was apparently reduced in the combination group compared with the control (P<0.05). However, expression of PD-L1 was significantly decreased after knockdown of p65 in IR group (P<0.05), but increased in the combination group (P<0.05) and slightly increased in CpG ODN-alone group (P<0.05), which was opposite to that without p65 knockdown group. CONCLUSION: This study demonstrated that radiotherapy combined with CpG ODN 7909 was able to downregulate PD-L1 expression through inhibition via the NF-κB signaling pathway. Dove Medical Press 2016-10-21 /pmc/articles/PMC5085295/ /pubmed/27799798 http://dx.doi.org/10.2147/OTT.S116629 Text en © 2016 Chen et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Chen, Xue
Zhang, Qi
Luo, Youjun
Gao, Caixia
Zhuang, Xibing
Xu, Guoxiong
Qiao, Tiankui
High-dose irradiation in combination with toll-like receptor 9 agonist CpG oligodeoxynucleotide 7909 downregulates PD-L1 expression via the NF-κB signaling pathway in non-small cell lung cancer cells
title High-dose irradiation in combination with toll-like receptor 9 agonist CpG oligodeoxynucleotide 7909 downregulates PD-L1 expression via the NF-κB signaling pathway in non-small cell lung cancer cells
title_full High-dose irradiation in combination with toll-like receptor 9 agonist CpG oligodeoxynucleotide 7909 downregulates PD-L1 expression via the NF-κB signaling pathway in non-small cell lung cancer cells
title_fullStr High-dose irradiation in combination with toll-like receptor 9 agonist CpG oligodeoxynucleotide 7909 downregulates PD-L1 expression via the NF-κB signaling pathway in non-small cell lung cancer cells
title_full_unstemmed High-dose irradiation in combination with toll-like receptor 9 agonist CpG oligodeoxynucleotide 7909 downregulates PD-L1 expression via the NF-κB signaling pathway in non-small cell lung cancer cells
title_short High-dose irradiation in combination with toll-like receptor 9 agonist CpG oligodeoxynucleotide 7909 downregulates PD-L1 expression via the NF-κB signaling pathway in non-small cell lung cancer cells
title_sort high-dose irradiation in combination with toll-like receptor 9 agonist cpg oligodeoxynucleotide 7909 downregulates pd-l1 expression via the nf-κb signaling pathway in non-small cell lung cancer cells
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085295/
https://www.ncbi.nlm.nih.gov/pubmed/27799798
http://dx.doi.org/10.2147/OTT.S116629
work_keys_str_mv AT chenxue highdoseirradiationincombinationwithtolllikereceptor9agonistcpgoligodeoxynucleotide7909downregulatespdl1expressionviathenfkbsignalingpathwayinnonsmallcelllungcancercells
AT zhangqi highdoseirradiationincombinationwithtolllikereceptor9agonistcpgoligodeoxynucleotide7909downregulatespdl1expressionviathenfkbsignalingpathwayinnonsmallcelllungcancercells
AT luoyoujun highdoseirradiationincombinationwithtolllikereceptor9agonistcpgoligodeoxynucleotide7909downregulatespdl1expressionviathenfkbsignalingpathwayinnonsmallcelllungcancercells
AT gaocaixia highdoseirradiationincombinationwithtolllikereceptor9agonistcpgoligodeoxynucleotide7909downregulatespdl1expressionviathenfkbsignalingpathwayinnonsmallcelllungcancercells
AT zhuangxibing highdoseirradiationincombinationwithtolllikereceptor9agonistcpgoligodeoxynucleotide7909downregulatespdl1expressionviathenfkbsignalingpathwayinnonsmallcelllungcancercells
AT xuguoxiong highdoseirradiationincombinationwithtolllikereceptor9agonistcpgoligodeoxynucleotide7909downregulatespdl1expressionviathenfkbsignalingpathwayinnonsmallcelllungcancercells
AT qiaotiankui highdoseirradiationincombinationwithtolllikereceptor9agonistcpgoligodeoxynucleotide7909downregulatespdl1expressionviathenfkbsignalingpathwayinnonsmallcelllungcancercells