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Aspirin promotes apoptosis and inhibits proliferation by blocking G0/G1 into S phase in rheumatoid arthritis fibroblast-like synoviocytes via downregulation of JAK/STAT3 and NF-κB signaling pathway
Title: | Aspirin promotes apoptosis and inhibits proliferation by blocking G0/G1 into S phase in rheumatoid arthritis fibroblast-like synoviocytes via downregulation of JAK/STAT3 and NF-κB signaling pathway |
Authors: | Zhang, X. Browse this author | Feng, H. Browse this author | Du, J. Browse this author | Sun, J. Browse this author | Li, D. Browse this author | Hasegawa, T. Browse this author →KAKEN DB | Amizuka, N. Browse this author →KAKEN DB | Li, Minqi Browse this author →KAKEN DB |
Keywords: | aspirin | fibroblast‑like synoviocytes | apoptosis | cell cycle | proliferation | NF‑κB | JAK/STAT3 |
Issue Date: | Dec-2018 |
Publisher: | Spandidos Publications |
Journal Title: | International journal of molecular medicine |
Volume: | 42 |
Issue: | 6 |
Start Page: | 3135 |
End Page: | 3148 |
Publisher DOI: | 10.3892/ijmm.2018.3883 |
Abstract: | Rheumatoid arthritis (RA) is a commonly occurring autoimmune disease. Its defining pathological characteristic is the excessive proliferation of fibroblast-like synoviocytes (FLS), which is similar to tumor cells and results in a range of clinical problems. As a commonly used antipyretic, analgesic and anti-inflammatory drug, aspirin is the first-line treatment for RA. However, its mechanism of action has not been well explained. The goal is to investigate the biological effects of aspirin on primary RA-FLS and its underlying mechanisms. In this experiment we treated cells with various concentrations of aspirin (0, DMSO, 1, 2, 5, 10 mM). Cell proliferation activity was detected with CCK-8 assays. Apoptosis and cell cycle distribution were detected via flow cytometry. Apoptosis and cell cycle-associated proteins (Bcl-2, Bax, PRAP1, Cyclin D1, P21), as well as the key proteins and their phosphorylation levels of the NF-κB and JAK/STAT3 signaling pathways, were detected via western blot analysis. Bioinformatics prediction revealed that aspirin was closely associated with cell proliferation and apoptosis, including the p53 and NF-κB signaling pathways. By stimulating with aspirin, cell viability decreased, while the proportion of apoptotic cells increased, and the number of cells arrested in the G0/G1 phase increased in a dose-dependent manner. The expression of Bax increased with aspirin stimulation, while the levels of Bcl-2, PRAP1, Cyclin D1 and P21 decreased; p-STAT3, p-P65 and p-50 levels also decreased while STAT3, P65, P50, p-P105 and P105 remained unchanged. From our data, it can be concluded that aspirin is able to promote apoptosis and inhibit the proliferation of RA-FLS through blocking the JAK/STAT3 and NF-κB signaling pathways. |
Type: | article |
URI: | http://hdl.handle.net/2115/72295 |
Appears in Collections: | 歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 長谷川 智香
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