Objective      To determine the effect of metformin on the proliferation and apoptosis in the synoviocytes isolated from the patients with rheumatoid arthritis.   Methods      The synovial tissues were collected from rheumatoid arthritis patients

and then digested by trypsin to isolated synoviocytes. CCK-8 assay and flow cytometry were employed to detect the cell proliferation in the synoviocytes after treated by metformin at the concentrations of 10

20 and 30 mmol/L. TUNEL assay and flow cytometry were used to measure the cell apoptosis after treatment. The contents of inflammatory factors and anti-inflammatory factors (TNF-α

IL-6

IL-1β and IL-10) in the supernatant were determined by ELISA.  Results      Metformin treatment (10

20

30 mmol/L) for 24

48 or 72 h inhibited the proliferation of synoviocytes in concentration- and time-dependent manners. CCK8 assay indicated that 20 and 30 mmol/L metformin significantly inhibited the proliferation of synoviocytes (P0.05). Flow cytometry showed that 20 mmol/L metformin treatment for 48 h increased the percentage of the cells at G0/G1 phase by 20% when compared with the control group (P0.05)

while decreased the percentages of synoviocytes at G2/M and S phases by 9% and 11% respectively (P0.05). Metformin treatment (20 and 30 mmol/L) for 48 and 72 h significantly enhanced the apoptotic rate (by 17.5%) compared with the control group (P0.05). The contents of TNF-α

IL-6 and IL-1β was markedly suppressed after metformin treatment of 20 and 30 mmol/L (P0.05)

and the treatment elevated the IL-10 level by 66% and 76% respectively (P0.05).  Conclusion      Metformin can suppresse the proliferation and induce the apoptosis of synoviocytes isolated from rheumatoid arthritis patients

and these effects may contribute to the decreases of TNF-α

IL-6

IL-1β and the elevation of IL-10.