The mechanism of arsenic trioxide on apoptosis of human flbroblast-like synoviocytes of rheumatoid arthritis

Objective To observe the effects of arsenic trioxide (ATO) on apoptosis of human fibrob- last-like synoviocytes of rheumatoid arthritis (HFLS-RA) and to study the mechanism.Methods HFLS-RA were cultured with standard medium as control group or with mediums supplemented with 0.5,2,8μmol/L ATO respectively.The apoptosis of HFLS-RA cultured for 72 h with different concentrations of ATO were in- vestigated under electron microscope.Apoptosis exponent was measured by terminal deoxynucleotidyl transf erase-mediated dUTP nick-end labeling (TUNEL).To detect the proliferation of HFLS-RA euhured with ATO,MTr assay were carded out in 5 consecutive days.Moreover,the NF-kB mRNA level of HFLS-RA was measured by RT-PCR after treated with ATO for 24 h.Results ATO induced the apoptosis of HFLS-RA. Apoptosis exponent was increased in a dose dependent manner in TUNEL experiment,especially in the cells treated with 2 and 8μmol/L ATO (P＜0.05).HFLS-RA proliferation was inhibited in both dose and time de- pendent manner when cultured with ATO.Meanwhile,the NF-kB mRNA level was decreased in ATO treated groups,which was especially significant in mediums cultured in higher than 2μmol/L ATO (P＜0.05).Con- clusion ATO depresses the proliferation of HFLS-RA and may increase the apoptosis by decreasing the ex- pression of NF-kB mRNA.These findings suggest that ATO have the potential to be a novel therapeutic agents for rheumatoid arthritis.