|Table of Contents|

EZH2 regulates cell growth and cytokine expression in non-small cell lung cancer through ROS/p38 MAPK phosphorylation pathway

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 20
Page:
3715-3721
Research Field:
Publishing date:

Info

Title:
EZH2 regulates cell growth and cytokine expression in non-small cell lung cancer through ROS/p38 MAPK phosphorylation pathway
Author(s):
LI Yao; HU Qun
Department of Oncology,Affiliated Hospital of Inner Mongolia Medical University,Inner Mongolia Hohhot 010050,China.
Keywords:
non-small cell lung cancer; enhancer of Zeste homolog 2; proliferation; immune escape
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2023.20.001
Abstract:
Objective:To explore the effect and mechanism of enhancer of Zeste homolog 2 (EZH2) on cell growth and cytokine expression in non-small cell lung cancer (NSCLC).Methods:EZH2 protein expression in NSCLC tissues and normal tissues at tumor margins was observed by immunohistochemical staining.Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to determine EZH2 mRNA expression in human NSCLC cell lines and normal lung epithelial cell line.A549 cells were divided into control group,GSK126 group,ROS inhibitor (NAC)+GSK126 group,SB203580+GSK126 group.After the corresponding treatment,MTT assay,EdU staining and cell clonal formation assay were used to detect the cell proliferation in each group.The contents of vascular endothelial growth factor (VEGF),interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in the supernatant of cell culture medium in each group were determined by enzyme-linked immunosorbent assay (ELISA).DCFH-DA fluorescence probe was used to detect the levels of intracellular reactive oxygen species (ROS),and the phosphorylation levels of p38 mitogen activated protein kinase (p38 MAPK) were determined by Western blot.Results:The positive expression rate of EZH2 in NSCLC tissues was significantly higher than that in tumor margin normal tissues (P＜0.05).The relative expression level of EZH2 mRNA in human NSCLC cell lines A549,HCC827,H1975,H1299 and SPC-A-1 was significantly higher than that in normal lung epithelial cell line BEAS-2B (P＜0.05).Compared with the control group,the cell survival rate and the positive rate of EdU in GSK126 group were significantly decreased (P＜0.05),the number of cell clone formation was significantly decreased (P＜0.05),the contents of immune factors VEGF,IFN-γ and TNF-α in the supernatant of cell culture medium were significantly decreased (P＜0.05),but the intracellular ROS levels and phosphorylation levels of p38 MAPK were significantly increased (P＜0.05).Compared with GSK126 group,the cell survival rate and the positive rate of EdU in NAC+GSK126 group and SB203580+GSK126 group were significantly increased (P＜0.05),and the number of cell clones formed was significantly increased (P＜0.05),the contents of immune factors VEGF,IFN-γ and TNF-α in the supernatant of cell culture medium were significantly increased (P＜0.05),while the levels of intracellular ROS and phosphorylation of p38 MAPK were significantly decreased (P＜0.05).Conclusion:EZH2 is highly expressed in NSCLC and promotes the growth of tumor cells and the secretion of VEGF,IFN-γ,TNF-α,which may be related to the regulation of ROS/p38 MAPK phosphorylation pathway.

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Memo

Memo:
内蒙古自治区自然科学基金项目（编号：2021LHMS08046）
Last Update: 1900-01-01