In Vitro Effects of a Small-Molecule Antagonist of the Tcf/ß-Catenin Complex on Endometrial and Endometriotic Cells of Patients with Endometriosis
نویسندگان
چکیده
BACKGROUND Our previous studies suggested that aberrant activation of Wnt/ß-catenin signaling might be involved in the pathophysiology of endometriosis. We hypothesized that inhibition of Wnt/ß-catenin signaling might result in inhibition of cell proliferation, migration, and/or invasion of endometrial and endometriotic epithelial and stromal cells of patients with endometriosis. OBJECTIVES The aim of the present study was to evaluate the effects of a small-molecule antagonist of the Tcf/ß-catenin complex (PKF 115-584) on cell proliferation, migration, and invasion of endometrial and endometriotic epithelial and stromal cells. METHODS One hundred twenty-six patients (78 with and 48 without endometriosis) with normal menstrual cycles were recruited. In vitro effects of PKF 115-584 on cell proliferation, migration, and invasion and on the Tcf/ß-catenin target genes were evaluated in endometrial epithelial and stromal cells of patients with and without endometriosis, and in endometrial and endometriotic epithelial and stromal cells of the same patients. RESULTS The inhibitory effects of PKF 115-584 on cell migration and invasion in endometrial epithelial and stromal cells of patients with endometriosis prepared from the menstrual phase were significantly higher than those of patients without endometriosis. Levels of total and active forms of MMP-9 were significantly higher in epithelial and stromal cells prepared from menstrual endometrium in patients with endometriosis compared to patients without endometriosis. Treatment with PKF 115-584 inhibited MMP-9 activity to undetectable levels in both menstrual endometrial epithelial and stromal cells of patients with endometriosis. The number of invasive cells was significantly higher in epithelial and stromal cells of endometriotic tissue compared with matched eutopic endometrium of the same patients. Treatment with PKF 115-584 decreased the number of invasive endometriotic epithelial cells by 73% and stromal cells by 75%. CONCLUSIONS The present findings demonstrated that cellular mechanisms known to be involved in endometriotic lesion development are inhibited by targeting the Wnt/β-catenin pathway.
منابع مشابه
Involvement of the Wnt/β-Catenin Signaling Pathway in the Cellular and Molecular Mechanisms of Fibrosis in Endometriosis
BACKGROUND During the development and progression of endometriotic lesions, excess fibrosis may lead to scarring, chronic pain, and altered tissue function. However, the cellular and molecular mechanisms of fibrosis in endometriosis remain to be clarified. OBJECTIVES The objective of the present study was to investigate whether the Wnt/β-catenin signaling pathway was involved in regulating th...
متن کاملApoptosis induction of human endometriotic epithelial and stromal cells by noscapine
Objective(s): Endometriosis is a complex gynecologic disease with unknown etiology. Noscapine has been introduced as a cancer cell suppressor. Endometriosis was considered as a cancer like disorder, The aim of present study was to investigate noscapine apoptotic effect on human endometriotic epithelial and stromal cells in vitro. Materials and Methods:In this in vitro study, endometrial biopsie...
متن کاملP-111: Inhibitory Effect of Noscapine on Human Endometriotic Epithelial Cells
Background: Endometriosis is the presence of a functional endometrial tissue outside the uterine cavity and defines as cancer like model. Noscapine is a safe cough suppressant which has been introduced as cancer suppressor. The aim of this study was to investigate the in vitro effect of noscapine on human endometriotic epithelial cells. Materials and Methods: Human endometriotic biopsies (n=7) ...
متن کاملin vitro Anti-Proliferative Effect of Adiponectin on Human Endometriotic Stromal Cells through AdipoR1 and AdipoR2 Gene Receptor Expression
Background: Endometriosis is a complex disorder in reproductive age women which consist of stromal and epithelial cells implantation outside the uterine cavity. Adiponectin is a member of cytokine family with various metabolic roles and proliferation inhibition of many cancer cells. The aim of the present research was to determine adiponectin effect on human endometriotic stromal cells (ESCs) p...
متن کاملP-136: High Concentrations of Noscapine Induces Apoptosis in Stromal Cells of Endometriosis In Vitro
Background: Endometriosis is a benign hormone-dependent disease in women of reproductive age. There is no cure for eradicating the disease and there is need for new drugs. The aim of this study was to investigate the in vitro effect of noscapine as inducer of cell death on endometriotic stromal cells in patient's endometriosis in vitro. Materials and Methods: Endometrial biopsies from pati...
متن کامل