Activation of PTGS2/NF‐κB signaling pathway enhances radiation resistance of glioma

Cheng Tan,Yimeng Dai,Guifang Zhao,Libo Wang,Liang Liu,Ling Qi,Xiaoyang Liu,Weiyao Wang

doi:10.1002/cam4.1971

Abstract

ObjectiveWe focused on the effects of PTGS2/NF‐κB signaling pathway on the radiation resistance of glioma in the study.MethodsWe downloaded the microarray data from the Gene Expression Omnibus (GEO) database. We verified transfection successfully through QRT‐PCR analysis. Immunofluorescence was used to detect γH2AX content under 2 Gy radiation. The survival rates of cells under 2 Gy irradiation were tested by clonogenic survival assay. Flow cytometry was used to detect cell cycle. Western blot was applied to detect the expression of NF‐κB pathway‐related proteins. We also used MTT assay to detect the proliferation of cells.ResultsIn this research, we discovered that the expression of the PTGS2 was upregulated in radiation‐resistant glioma cells. The radio‐tolerance rate of U87 cells was obviously elevated after the overexpression of PTGS2. The radioresistance of U87R cells was significantly reduced after the knockdown of PTGS2. After radiotherapy, the number of cells arrested in G2/M phase decreased after PTGS2 overexpression in U87cells but increased in PTGS2 knockdown in U87R cells. The survival rate of U87 and U87R cells under radiation decreased significantly after the addition of NF‐κB inhibitor. The proliferation of U87 cells was suppressed by radiation and the addition of Bay 11. In addition, PTGS2 activated NF‐κB signaling pathway and prevented DNA damage after radiotherapy. Lastly, PTGS2 was proved to facilitate tumor cell proliferation and improve the radio‐tolerance.Conclusion PTGS2/NF‐κB signaling pathway was involved in radio‐tolerance of glioma cells, which provided a new insight into glioma therapy.

Highlights

Glioma is the most common malignant cancer in the central nervous system in adults
We found that the radio‐tolerance of U87 cells was significantly increased after the overexpression ofPTGS2 compared with the group in which PTGS2 was knocked down
PTGS2 was reported to be overexpressed in cancer cells and associated with the resistance of cancer cells to IR.[23]

Summary

| INTRODUCTION

Glioma is the most common malignant cancer in the central nervous system in adults. Most patients with glioma could live for only a few months without treatment.[1]. Reactive oxygen species produced in radiotherapy induces a variety of DNA lesions, including oxidized base damage, single‐strand breaks (SSBs), and double‐strand breaks (DSBs). These lesions may result in cell death through mitotic catastrophe and apoptosis.[3]. We linked PTGS2 with NF‐κB signaling pathway, which is closely related to cancer cell proliferation and radiotherapy tolerance. We sought to investigate PTGS2 upregulation to explore the ability of NF‐κB signaling on the regulation of glioma cell activities. We hypothesized that NF‐ κB signaling pathway could influence radiotherapy tolerance of glioma cells through regulating PTGS2, which may imply potential therapeutic approaches for the treatment of glioma

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Findings

| DISCUSSION