Sorafenib inhibits ovarian inflammation and fibrosis in polycystic ovary syndrome by targeting the PDGFA/PDGFRα/NF-κB pathway in granulosa cells

Abstract The etiology of polycystic ovary syndrome (PCOS) remains unknown. However, emerging evidence is increasingly suggesting that ovarian inflammation and fibrosis are among the primary causes of pathological changes. Sorafenib is a multiple kinases inhibitor that targets receptor tyrosine kinases including vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR). Sorafenib was found to inhibit the activation of nuclear factor kappa B (NF-κB). However, the effects of sorafenib on PCOS ovarian inflammation and fibrosis remained unknown. Our findings demonstrated that sorafenib effectively inhibited the PDGFA/PDGFRα axis, which subsequently led to the suppression of NF-κB activation. This inhibition further resulted in a decrease in chemokine expression, thereby impeding the recruitment and polarization of macrophages. Consequently, this process resulted in the down-regulation of collagen deposition. These results provide a new perspective and direction for the clinical treatment of PCOS.