Abstract: Objective To investigate the effect and possible mechanism of arsenic trioxid（As2O3）on proliferation of RSC-364 synoviocyte lines stimulated with TNFα. Methods RSC-364 synoviocytes were cultured with standard medium as control group or medium supplemented with 10μg/LTNFα and different concentration As2O3 respectively. MTT assay were carried out to study cell proliferation. Proliferation index (PI) and cell cycle were detected by flow cytometry (FCM). RT-PCR was used to detect the mRNA expression of High mobility group box chromosomal protein (HMGB)1. HMGB1and proliferation cell nuclear antigen (PCNA) proteins were detected by immunocytochemistry and FCM; Results ①As2O3 could inhibit proliferation of cell lines stimulated by TNFα in time-dependent and dose-dependent. ② Compared with normal group, TNFα could up-regulated HMGB1 protein and mRNA as well as PCNA protein. HMGB1 protein were not only in nuclear but also in cytoplasm by immunocytochemistry. As2O3 could down-regulated mRNA and protein of HMGB1 in a dose-dependent; so did PCNA proteins (P<0.01). ③Compared with TNFα stimulation group, G0/G1 phase cell percentage increased and G2/ M phase decreased with the increasing As2O3 concentrations. PI also remarkably decreased (P<0.01).④ There was positive correlation between HMGB1 and PCNA(r=0.946, P﹤0.001). Moreover both of them were also with positive correlation to PI (r=0.731, P﹤0.001; r=0.706 P﹤0.001). Conclusion Arsenic trioxide could inhibit synoviocyte proliferation stimulated with TNFα. which maybe correllated with down-regulating expression of HMGB1 and blocking cell cycle.

Key words: Arthritis, Rheumatoid, Synoviocytes, Arsenicals, High mobility group box chromosomal protein 1