Date: Monday, October 22, 2018
Session Title: Rheumatoid Arthritis – Etiology and Pathogenesis Poster II
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Fibroblast-like synoviocytes (FLS) play important roles on joint destruction in rheumatoid arthritis (RA). Recent reports showed that antimalaria drug artesunate presents anti-cancer potential by suppressing cancer cells invasion and metastasis. We have found that artesunate could inhibit migration and invasion of RA-FLS as well as MMP-2/9 expression. Methotrexate (MTX) is the anchor drug for RA treatment. Here we aimed to investigate the synergistic effect of artesunate with MTX on inhibiting aggressive ability of RA-FLS.
Methods: Synovial tissues were obtained by closed needle biopsy from 6 active RA patients and FLS were isolated. Primary RA-FLS were cultured in vitro and pretreated with 60¦ÌM artesunate, 10nM MTX, or combination of 60¦ÌM artesunate and 2.5nM~10nM MTX respectively for indicated times. Their effects on cell viability and proliferation were measured by CCK-8 assay, while effects on migration and invasion capacity of RA-FLS were detected by wound healing and transwell assays. Differential expression of MMP-2/9 and tissue inhibitors of metalloproteinases (TIMP) -1/2 were detected by quantitative real-time PCR, western blot and ELISA.
Results: (1) Compared with untreated group, 60¦ÌM artesunate, 10nM MTX or combination of 60¦ÌM artesunate and 2.5nM~10nM MTX showed no significant effect on cell viability and proliferation of RA-FLS for 72 hours (Fig 1A). (2) Both 60¦ÌM artesunate and10nM MTX alone significantly inhibited migration and invasion of RA-FLS. The combination of 60¦ÌM artesunate and 7.5nM MTX had stronger inhibitory effect on migration and invasion than 60¦ÌM artesunate or 10nM MTX alone (Fig 1B). (3) Both 60¦ÌM artesunate and10nM MTX alone significantly inhibited MMP-2/9 expression but promoted the expression of TIMP-2. The combination of 60¦ÌM artesunate and 7.5nM MTX had stronger effect on regulating MMP-9 and TIMP-2 than 60¦ÌM artesunate or 10nM MTX alone (Fig 1C).
Conclusion: Artesunate can synergize with MTX on inhibiting migration and invasion of primary RA-FLS by inhibiting MMP-9 and promoting TIMP-2 expression, which implies the potential of combination therapy of artesunate and MTX for RA.
Fundings: This work was supported by National Natural Science Foundation of China (no. 81471597, 81671612), Guangdong Natural Science Foundation (no. 2017A030313576, 2017A030310236) and Scientific Program of Traditional Chinese Medicine Bureau of Guangdong Province (no. 20161058, 20181058).
To cite this abstract in AMA style:Ma JD, Jing J, Wang JW, Yan T, Mou YS, Mo YQ, Dai L. Artesunate Can Synergize with Methotrexate on Inhibiting Migration and Invasion of Fibroblast-like Synoviocytes from Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/artesunate-can-synergize-with-methotrexate-on-inhibiting-migration-and-invasion-of-fibroblast-like-synoviocytes-from-patients-with-rheumatoid-arthritis/. Accessed April 8, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/artesunate-can-synergize-with-methotrexate-on-inhibiting-migration-and-invasion-of-fibroblast-like-synoviocytes-from-patients-with-rheumatoid-arthritis/