Regulation of CP-25 on P-glycoprotein in synoviocytes of rats with adjuvant arthritis - 01/10/19
, Wei Wei a, b, c, ⁎ Bienvenue sur EM-consulte, la référence des professionnels de santé.
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Highlights |
• | CP-25 had a therapeutic effect on AA rats and the treatment of MTX combined with CP-25 was better than MTX alone. |
• | CP-25 could inhibit TNF-α-induced P-gp expression in synoviocytes. |
• | CP-25 could regulate the P-gp to reverse the resistance of Bel7402/5-FU resistant cells to MTX. |
• | CP-25 could be potential to reverse MTX resistance in RA therapy. |
Abstract |
Objective |
Methotrexate (MTX) is a commonly used drug for the treatment of rheumatoid arthritis (RA) and it has been studied in RA resistance recently. P-glycoprotein (P-gp) is one of the important transporters that mediate MTX resistance. This study investigated the effect of Paeoniflorin-6′-O-benzene sulfonate (code: CP-25) in the resistance of P-gp-mediated MTX to RA.
Methods |
Adjuvant arthritis (AA) was induced in rats via complete Freund’s adjuvant. The experimental groups were divided into normal group; AA model group; monotherapy groups, including CP-25, MTX and dexamethasone; and CP-25 combined with MTX group. The expression of P-gp in synovial tissue was measured by western blot and histochemistry. Besides, P-gp high expression of human hepatoma cell line Bel7402/5-FU and Bel7402 were chose to study in MTX resistance and the function of P-gp was detected by Flow cytometry.
Results |
CP-25 had a good therapeutic effect on AA rats, significantly improved manifestations and reduced the expression of P-gp in synovial tissue, spleen medulla and small intestinal epithelial cells in the apical tissues of AA rats. In addition, CP-25 significantly inhibited the up-regulation of P-gp induced by TNF-α stimulation in synoviocytes. Furthermore, according to the accumulation and efflux of rhodamine 123 in Bel7402/5-FU resistant cells and Bel7402 sensitive cells, CP-25 could reverse the resistance of MTX in Bel7402/5-FU cells compared with Bel7402 cells, which was reflected by the reduced IC50 values of MTX. Further study indicated that CP-25 could decrease P-gp expression and inhibit P-gp function in Bel7402/5-FU cells.
Conclusion |
CP-25 regulates the expression of P-gp and inhibits the function of P-gp, thereby improving the resistance of MTX.
Le texte complet de cet article est disponible en PDF.Keywords : Methotrexate, P-glycoprotein, Paeoniflorin-6′-O-benzene sulfonate, Adjuvant arthritis, Resistance
Plan
Vol 119
Article 109432- novembre 2019 Retour au numéro
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