Capilliposide from Lysimachia capillipes promotes terminal differentiations and reverses paclitaxel resistance in A2780T cells of human ovarian cancer by regulating Fos/Jun pathway

Objective:To investigate the potential effect of Lysimachia capillipes capilliposide(LCC)on the chemo sensitivity and the stemness of human ovarian cancer cells.Methods:Cell Counting Kit-8(CCK8)was used to measure the IC50 values.The apoptosis of cells was measured through flow cytometry.Evaluation of the stemness and differentiation markers was performed by the immunoblotting and the immunostaining assays.RNA-seq was performed through the Illumina HiSeq PE150 platform and differentially expressed genes(DEGs)were screened out through the bioinformation analysis.Overexpression or knockdown of Fos gene was achieved by shRNA transfection.Results:Pre-exposure of A2780T cells with 10μg/mL LCC sensitized them to paclitaxel,of which the IC50 value reduced from 8.644μmol/L(95%CI:7.315–10.082μmol/L)to 2.5μmol/L(95%CI:2.233–2.7882μmol/L).Exposure with LCC enhanced the paclitaxel-induced apoptosis and inhibited the colony formation of A2780T cells.LCC exposure reduced the expression of cancer stemness markers,ALDH1,Myd88 and CD44,while promoting that of terminal differentiation markers,NFATc1,Cathepsin K and MMP9.RNAseq analysis revealed that the expressions of FOS and JUN were upregulated in LCC-treated A2780T cells.A2780T cells overexpressing Fos gene displayed increased paclitaxel-sensitivity and reduced cell stemness,and shared common phenotypes with LCC-treated A2780T cells.Conclusion:These findings suggested that LCC promoted terminal differentiations of ovarian cancer cells and sensitized them to paclitaxel through activating the Fos/Jun pathway.LCC might become a novel therapy that targets at cancer stem cells and enhances the chemotherapeutic effect of ovarian cancer treatments.