OBJECTIVETo investigate the effects of triptolide on proliferation and regulation of ras-MAPKs pathway in human fibroblast-like synoviocytes of rheumatoid arthritis (RA-HFLS) treated with tumor necrosis factor (TNF-alpha).

METHODRA-HFLS were cultured with TNF-alpha in the presence or absence of variable doses of triptolide (0.28, 2.8, 28, 140 nmol x L(-1)) in vitro. Cell proliferation was evaluated by MTS assay. The phosphorylation status of Ras-MAPKs-associated proteins (Ras, p-P38, p-ERK and p-JNK) were detected by Western blot analysis.

RESULTTriptolide could obviously decrease the RA-HFLS viability in a dose-dependent manner and the inhibition ratio was 0.28%, 5.05%, 30.83% and 43.77% respectively. In addition, triptolide could also suppressed the expression of Ras, p-P38, p-ERK and p-JNK.

CONCLUSIONTriptolide has an notable inhibiting effect on proliferation of RA-HFLS and the molecule mechanism is due in part to the direct suppression of abnormal activation of Ras-MAPKs pathway.

Animals ; Cell Line ; Cell Proliferation ; drug effects ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Gene Expression Regulation ; drug effects ; MAP Kinase Signaling System ; drug effects ; Mice ; Mitogen-Activated Protein Kinases ; metabolism ; Phenanthrenes ; pharmacology ; Synovial Membrane ; cytology ; drug effects ; metabolism ; Tumor Necrosis Factor-alpha ; pharmacology ; ras Proteins ; metabolism