Effects of paclitaxel on cultured synovial cells from patients with rheumatoid arthritis.
BACKGROUND
Proliferation of synovial cells is considered to play a key role in rheumatoid arthritis (RA). Using paclitaxel, a unique antineoplastic agent known to suppress collagen-induced arthritis, we conducted an in vitro study of cell kinetics on cultured synovial cells from patients with RA.


METHODS
Alterations of the cell cycle of cultured fibroblast-like synovial cells (FLSs) from patients with RA were studied using flow cytometry and laser scanning cytometry. Apoptosis and accumulation of cyclin concerning effects of paclitaxel were detected.


RESULTS
Paclitaxel induced arrest of the cell cycle at G2/M phase and apoptosis in FLSs. The late stage of apoptosis was determined by the positivity of terminal deoxynucleotidyl transferase assay. Morphological observation by combined usage of both annexin V and propidium iodide on FLSs on a slide glass showed early apoptotic changes in detail. FLSs arrested at G2/M phase showed marked accumulation of cyclin B1. The effects of paclitaxel decreased on FLSs, which diminished proliferative activity.


CONCLUSIONS
These data indicate that paclitaxel induces cell arrest at G2/M phase followed by apoptosis in human FLSs, which have high proliferative activity, and possible therapeutic effects of paclitaxel on RA.
Kurose
A
A
Department of Pathology, Iwate Medical University, Morioka, Japan. akurose@iwate-med.ac.jp
Yoshida
W
W
Yoshida
M
M
Sawai
T
T
D000328:Adult; D000368:Aged; D017304:Annexin A5 / Q000032:analysis; D017209:Apoptosis / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000503:physiopathology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology; D019926:Cyclin B / Q000187:drug effects*; D056744:Cyclin B1; D005260:Female; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling / Q000379:methods; D017746:Joint Capsule / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008938:Mitosis / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology*; D011419:Propidium / Q000032:analysis
D017304:Annexin A5; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D011419:Propidium; D017239:Paclitaxel