Synergistic Effect of NF-κB Signaling Pathway Inhibitor and Oncolytic 
Measles Virus Vaccine Strain against Lung Cancer and Underlying Mechanisms

Background and objective Lung cancer is one of the leading causes of cancer-related morbidity and mortality. Oncolytic virotherapy is an emerging therapeutic modality that utilizes replication-competent viruses to destroy cancers. As a powerful tool to kill tumor cells with excellent safety profile,...

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Main Authors: Mao XIA, Gang MENG, Jie DONG
Format: Article
Language:zho
Published: Chinese Anti-Cancer Association; Chinese Antituberculosis Association 2021-04-01
Series:Chinese Journal of Lung Cancer
Subjects:
Online Access:http://dx.doi.org/10.3779/j.issn.1009-3419.2021.102.14
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author Mao XIA
Gang MENG
Jie DONG
author_facet Mao XIA
Gang MENG
Jie DONG
author_sort Mao XIA
collection DOAJ
description Background and objective Lung cancer is one of the leading causes of cancer-related morbidity and mortality. Oncolytic virotherapy is an emerging therapeutic modality that utilizes replication-competent viruses to destroy cancers. As a powerful tool to kill tumor cells with excellent safety profile, attenuated measles virus of the Edmonston strain (MV-Edm) has been widely applied in the development of tumor therapy and preclinical trials. The aim of this study was to investigate the synergistic effect of nuclear factor kappa B (NF-κB) signaling pathway inhibitor and oncolytic measles virus vaccine against lung cancer and the involved mechanisms. Methods Using Western blot to detect MV-Edm infection of A549 and H1299 were infected by MV-Edm alone or used the NF-κB pathway inhibitor PS1145/cell autophagy related siRNA, expression level of p-IκBα, IκBα, PARP and BAX were determined by western blot. Using flow cytometry to analysis the rate of apoptosis, and using MTT [3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide] method to detect the cell survival rate. Results Inhibition of cell autophagy could obviously inhibit the MV-Edm infection induced the NF-κB pathway activation in A549 and H1299. In MV-Edm infected A549 and H1299, p-IκBα level increased and IκBα level decreased over infection time, compared with control group. Inhibition of the NF-κB pathway by PS1145 could promote the apoptosis of MV-Edm infected A549 and H1299 and amplify the tumor killing effect. Conclusion The combination of NF-κB signaling pathway inhibitor pS1145 and oncolytic measles virus vaccine strains can promote the apoptosis of human lung cancer cells A549 and H1299 and enhance their oncolytic effect.
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spelling doaj.art-9d47adb3458847e595d3e4722d31d09a2022-12-21T23:08:28ZzhoChinese Anti-Cancer Association; Chinese Antituberculosis AssociationChinese Journal of Lung Cancer1009-34191999-61872021-04-0124424525310.3779/j.issn.1009-3419.2021.102.14Synergistic Effect of NF-κB Signaling Pathway Inhibitor and Oncolytic 
Measles Virus Vaccine Strain against Lung Cancer and Underlying MechanismsMao XIA0Gang MENG1Jie DONG2Department of Laboratory Medicine, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210007, ChinaDepartment of Laboratory Medicine, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210007, ChinaDepartment of Laboratory Medicine, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210007, ChinaBackground and objective Lung cancer is one of the leading causes of cancer-related morbidity and mortality. Oncolytic virotherapy is an emerging therapeutic modality that utilizes replication-competent viruses to destroy cancers. As a powerful tool to kill tumor cells with excellent safety profile, attenuated measles virus of the Edmonston strain (MV-Edm) has been widely applied in the development of tumor therapy and preclinical trials. The aim of this study was to investigate the synergistic effect of nuclear factor kappa B (NF-κB) signaling pathway inhibitor and oncolytic measles virus vaccine against lung cancer and the involved mechanisms. Methods Using Western blot to detect MV-Edm infection of A549 and H1299 were infected by MV-Edm alone or used the NF-κB pathway inhibitor PS1145/cell autophagy related siRNA, expression level of p-IκBα, IκBα, PARP and BAX were determined by western blot. Using flow cytometry to analysis the rate of apoptosis, and using MTT [3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide] method to detect the cell survival rate. Results Inhibition of cell autophagy could obviously inhibit the MV-Edm infection induced the NF-κB pathway activation in A549 and H1299. In MV-Edm infected A549 and H1299, p-IκBα level increased and IκBα level decreased over infection time, compared with control group. Inhibition of the NF-κB pathway by PS1145 could promote the apoptosis of MV-Edm infected A549 and H1299 and amplify the tumor killing effect. Conclusion The combination of NF-κB signaling pathway inhibitor pS1145 and oncolytic measles virus vaccine strains can promote the apoptosis of human lung cancer cells A549 and H1299 and enhance their oncolytic effect.http://dx.doi.org/10.3779/j.issn.1009-3419.2021.102.14oncolytic measles virus vaccine strainautophagynf-κb pathwayapoptosis
spellingShingle Mao XIA
Gang MENG
Jie DONG
Synergistic Effect of NF-κB Signaling Pathway Inhibitor and Oncolytic 
Measles Virus Vaccine Strain against Lung Cancer and Underlying Mechanisms
Chinese Journal of Lung Cancer
oncolytic measles virus vaccine strain
autophagy
nf-κb pathway
apoptosis
title Synergistic Effect of NF-κB Signaling Pathway Inhibitor and Oncolytic 
Measles Virus Vaccine Strain against Lung Cancer and Underlying Mechanisms
title_full Synergistic Effect of NF-κB Signaling Pathway Inhibitor and Oncolytic 
Measles Virus Vaccine Strain against Lung Cancer and Underlying Mechanisms
title_fullStr Synergistic Effect of NF-κB Signaling Pathway Inhibitor and Oncolytic 
Measles Virus Vaccine Strain against Lung Cancer and Underlying Mechanisms
title_full_unstemmed Synergistic Effect of NF-κB Signaling Pathway Inhibitor and Oncolytic 
Measles Virus Vaccine Strain against Lung Cancer and Underlying Mechanisms
title_short Synergistic Effect of NF-κB Signaling Pathway Inhibitor and Oncolytic 
Measles Virus Vaccine Strain against Lung Cancer and Underlying Mechanisms
title_sort synergistic effect of nf κb signaling pathway inhibitor and oncolytic 
measles virus vaccine strain against lung cancer and underlying mechanisms
topic oncolytic measles virus vaccine strain
autophagy
nf-κb pathway
apoptosis
url http://dx.doi.org/10.3779/j.issn.1009-3419.2021.102.14
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AT jiedong synergisticeffectofnfkbsignalingpathwayinhibitorandoncolyticmeaslesvirusvaccinestrainagainstlungcancerandunderlyingmechanisms