Dataset Information

M2 macrophages reduce the effect of gefitinib by activating AKT/mTOR in gefitinib-resistant cell lines HCC827/GR.

ABSTRACT: BACKGROUND:The biological behavior of cells change after they develop drug resistance, and the degree of resistance will be affected by the tumor microenvironment. Here, we aimed to explore the changes in the biological behavior of tumors and to observe the differences in the release of cytokines and chemokines which can influence the tumor microenvironment. We also aimed to study how TKIs-resistant cell lines recruit macrophages to reduce the sensitivity of the cells following gefitinib administration. METHODS:We generated and maintained gefitinib-resistant cell lines to study the differences between gefitinib-sensitive cell lines according to clone formation, cell growth curve analysis, whole-exome sequencing, and qPCR ARRAY technology. We used the WNT/?-catenin inhibitor, WNT/?-catenin activator and overexpression ?-catenin lentivirus to observe the changes in CCL2. M2 macrophages and gefitinib-resistant cell lines HCC827/GR were cocultured to detect the viability gefitinib for inducing cell death. RESULTS:The proliferation and migratory activities were much more pronounced in HCC827/GR cells. CCL2 expression was also enhanced and regulated by ?-catenin in HCC827/GR. CCL2 promoted the chemotactic ability of M2 macrophages. M2 macrophages reduced the antitumor effect of gefitinib treatment by activating AKT/mTOR. CONCLUSIONS:Gefitinib-resistant cell lines have stronger proliferation and migration capabilities, and attract macrophages by releasing more CCL2 to reduce the sensitivity of cells to gefitinib.

SUBMITTER: Xiao F

PROVIDER: S-EPMC7606002 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

M2 macrophages reduce the effect of gefitinib by activating AKT/mTOR in gefitinib-resistant cell lines HCC827/GR.

Xiao Fengqi F Liu Ni N Ma Xinchun X Qin Jing J Liu Yanguo Y Wang Xiuwen X

Thoracic cancer 20200921 11

<h4>Background</h4>The biological behavior of cells change after they develop drug resistance, and the degree of resistance will be affected by the tumor microenvironment. Here, we aimed to explore the changes in the biological behavior of tumors and to observe the differences in the release of cytokines and chemokines which can influence the tumor microenvironment. We also aimed to study how TKIs-resistant cell lines recruit macrophages to reduce the sensitivity of the cells following gefitinib ...[more]

PMID: 32956565

Similar Datasets

Project description:BackgroundThe anti-inflammatory properties of the cannabinoid 2 receptor (CB2R) in injury and inflammatory diseases have been widely substantiated. Specifically, the anti-inflammatory effect of CB2R may be achieved by regulating macrophage polarisation. Several research findings suggested that the activation of CB2R could attenuate inflammation by reducing pro-inflammatory M1 macrophage polarisation and promoting anti-inflammatory M2 polarisation. However, considering CB2R inhibits fibrosis and M2 promotes fibrosis, that the activation of CB2R may lead to an increase in M2 macrophages seems contradictory. Therefore, we hypothesised that the activation of CB2R to attenuate inflammation is not achieved by up-regulating M2 macrophages.MethodsWe established an incised wound model using mouse skin and used this to evaluate the effect of CB2R agonists (JWH133 or GP1a) and an antagonist (AM630) on wound healing. At various post-injury intervals, we used western blot analysis, immunofluorescence staining, enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction assays to determine CB2R protein expression, M1/M2 macrophage infiltration, and the protein and gene expression of M1/M2-associated markers and cytokines in skin lesions.ResultsActivation of CB2R significantly reduced M1 macrophage infiltration and slightly increased M2 macrophage infiltration. Similarly, gene expression and protein levels of M1-associated markers and cytokines (interleukin [IL]-6, IL-12, CD86 and inducible nitric oxide synthase) were significantly down-regulated after CB2R agonist administration; in contrast, markers and cytokines were increased in the CB2R antagonist-treated group. Conversely, the administration of agonists slightly increased gene expression and protein levels of M2-associated markers and cytokines (IL-4, IL-10, CD206 and arginase-1 [Arg-1]); however, a statistical significance at most time points post-injury was not noted.ConclusionIn summary, our findings suggested that during incised skin wound healing in mice, increased levels of CB2R may affect inflammation by regulating M1 rather than M2 macrophage subtype polarisation. These results offer a novel understanding of the molecular mechanisms involved in the inhibition of inflammation by CBR2 that may lead to new treatments for cutaneous inflammation.

Dataset Information

M2 macrophages reduce the effect of gefitinib by activating AKT/mTOR in gefitinib-resistant cell lines HCC827/GR.

Publications

M2 macrophages reduce the effect of gefitinib by activating AKT/mTOR in gefitinib-resistant cell lines HCC827/GR.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets