P–285 Controlling semi-invasive activity of human endometriotic stromal cells by inhibiting NF-kB signaling pathway using aloe-emodin or aspirin

Abstract Study question Does inhibiting nuclear factor-kB (NF-kB) signaling by aloe-emodin (AE) or aspirin (Asp), as anti-inflammatory compounds, suppress the invasive activity of stage IV human endometriotic stromal cells? Summary answer Eutopic endometriotic stromal cells (EuESCs) seem to have a semi-invasive activity which is largely suppressed by AE or Asp. What is known already Inflammation and its master regulator, NF-kB, have been implicated in the development of endometriosis. Inhibition of NF-kB pathway using small molecules ameliorated disease progression and reduced the lesion size; nevertheless, underlying mechanism is not fully understood. Study design, size, duration In this cross-sectional study, a total of 8 infertile patients with proven endometriosis and 8 women without endometriosis (Control group) undergoing infertility treatment cycles, were enrolled between October 2018 and December 2019. The invasiveness of collected endometriotic stromal cells before and after treatment with AE or Asp, was analyzed and compared with the control group. Participants/materials, setting, methods The eutopic endometriotic and healthy endometrial biopsies were digested and the single cells were cultured. Gene and protein expression of proliferation, adhesion, and invasion markers of eutopic endometriotic stromal cells (EuESCs) with and without treatment with AE or Asp, as well as control endometrial stromal cells (CESCs) were analyzed using q-PCR and immunofluorescence staining, respectively. Cell migration capacity was assessed by wound closure assay. Main results and the role of chance We observed an association between NF-kB overexpression and higher proliferation/adhesion capacity in EuESCs. TNF-α, as a known NF-kB inducer, further potentiated this association. EuESCs at stage IV, displayed silent invasive and migratory behaviors. Pretreatment of EuESCs with AE or Asp significantly attenuated NF-kB expression and reduced proliferative, adhesive, invasive and migratory activity. Limitations, reasons for caution Due to some adverse effects observed following treatment with AE or Asp on the normal activity of EuESCs, more investigations on possible toxicity of the treatment, must be considered. Wider implications of the findings: We suggest that both Asp and AE (as potent NF-kB inhibitors) may be useful as a supplement to conventional endometriosis treatments. Trial registration number Not applicable