FABP5 inhibitor SBFI-26 regulates FOXM1 expression and Wnt signaling pathway in ovarian granulosa cell of patients with polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy among females of reproductive age. Due to its unclear etiopathogenesis, it is of vital significance to take a deeper understanding of molecular mechanisms underlying PCOS. Quantitative real-time PCR (RT-qPCR) and western blot were applied for detection of gene expression and protein expression individually. Cell Counting Kit-8 (CCK-8) and colony formation assays were used for the evaluation of cell proliferation while Caspase-3/9 activity was measured for the assessment of cell apoptosis. We found that FOXM1 was overexpressed in ovarian granulosa cell (OGC) of patients with PCOS. Functionally, upregulation of FOXM1 promotes the proliferative ability of PCOS-OGC cells. As for mechanism, FOXM1 exerts its functions in PCOS-OGC cell through activation of the Wnt signaling pathway. More importantly, a novel FABP5 inhibitor, SBFI-26, was verified to downregulate the expression of FOXM1 to impede the proliferation of PCOS-OGC cells. In addition, SBFI-26 inactivates Wnt signaling pathway in PCOS-OGC cells. FABP5 inhibitor SBFI-26 regulates FOXM1 expression and Wnt signaling pathway in OGC of patients with PCOS, which might provide a new perspective into PCOS treatment.

Keywords: FOXM1; Ovarian granulosa cell; Polycystic ovary syndrome; SBFI-26; Wnt signaling pathway.