Metformin inhibits the proliferation of rheumatoid arthritis fibroblast-like synoviocytes through IGF-IR/PI3K/AKT/m-TOR pathway

In this study, we demonstrated that metformin could inhibit the RA-FLS proliferation in dose- and time-dependent manner. Our cell viability MTT test and 5-ethynyl-2-deoxyuridine incorporation assay showed that metformin inhibited the RA-FLSs proliferation with a time- and concentration-dependent increase. More importantly, metformin induced G2/M cell cycle phase arrest in RA-FLS via the IGF-IR/PI3K/AKT/ m-TOR pathway and inhibited m-TOR phosphorylation through both the IGF-IR/PI3K/AKT signaling pathways thereby further upregulating and down-regulating p70s6k and 4E-BP1 phosphorylation, respectively; however, metformin was found not to induce apoptosis in RA-FLSs. In summary, these results demonstrate that metformin can effectively inhibit RA-FLS proliferation through inducing cell cycle and upregulating and down-regulating p70s6k and 4E-BP1 phosphorylation. Moreover, IGF-IR/PI3K/AKT m-TOR signaling pathway can be regulated by metformin. Our results indicate that metformin may provide a new way of thinking for the treatment of RA.
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research