2‐Methoxyestradiol inhibits the proliferation level in keloid fibroblasts through p38 in the MAPK/Erk signaling pathway

The MAPK/Erk signaling pathway is a classic pathway in cell proliferation. Our former study showed that keloid tissue revealed a higher proliferation level than physiological scars and normal skin. As a natural metabolite of estradiol, 2-methoxyestradiol (2ME2) showed an inhibition proliferation effect on tumor cells.In this study, the treatment effect of 2ME2 and its potential mechanisms are explored.Six keloid patients and six non-keloid patients were randomly selected from the Department of Plastic Surgery at our hospital during June 2021 to December 2021. Six groups were established: normal skin fibroblasts (N); keloid fibroblasts (K); keloid fibroblasts treated with 2ME2 (K + 2ME2); keloid fibroblasts treated with dimethyl sulfoxide (DMSO) (K + DMSO); keloid fibroblasts treated with doramapimod (K + IN); keloid fibroblasts treated with doramapimod (p38 inhibitor) and 2ME2 (K + IN+2ME2). The fibroblast activity and key factor expression of the MAPK/Erk signaling pathway were measured.In the results, 2ME2 significantly inhibited keloid fibroblast activity and key factor expression (except STAT1).The proliferation levels were reduced by both the p38 inhibitor and 2ME2, indicating 2ME2 may achieve an antiproliferation effect by targeting p38 in keloid fibroblasts.