Guizhi-Fuling formula inhibits ovarian cancer progression by targeting STAT3 signaling network

摘要

Objective:Ovarian cancer(OC)is the most lethal gynecological malignancy.Frequent peritoneal dissemination is the main cause of low survival rate.Guizhi-Fuling formula(GZFL)is a classical traditional Chinese herbal formula,and has been clinically used for treating ovarian cancer with good outcome.However,its therapeutic mechanism for treating OC has not been clearly elucidated.Methods:Network pharmacology analysis was used to predict potential molecular mechanisms of GZFL in treating OC.In vitro and in vivo analysis,including STAT3 KO/WT cells proliferation assay,scratch assay and antitumor efficacy study were performed to assess the biological activity of GZFL on targeting STAT3 in OC cells.Results:We generated a“GZFL target-OC-STAT3”gene interaction network,and predicted that GZFL is tightly associated with IL6/JAK/STAT3 signal pathway and cancer metastasis.Our preliminary data showed that GZFL inhibited OC cell proliferation in a STAT3 dependent manner.It suppressed cell migration and downregulated p-STAT3 expression.In a tumor bearing mouse model,GZFL displayed a safety profile.Conclusion:GZFL inhibits OC progression by targeting STAT3 signaling network.Our newly proposed pharmacological mechanisms of Guizhi-Fuling formula will provide a new insight for its clinical use in treating OC.