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

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.