title: Inhibition of STAT3 signaling as critical molecular event in resveratrol-suppressed ovarian cancer cells.
abstract: BACKGROUND
  Resveratrol exerts inhibitory effects on ovarian cancer cells, while its underlying mechanism and critical molecular target(s) have been lesser known. Activations of Wnt, Notch and STAT3 signaling are frequent in ovarian cancers/OCs and supposed to be important for OC formation and progression, while the impacts of resveratrol on these signaling pathways in OC cells remain obscure.
  
  
  METHODS
  In this study, two human ovarian cancer cell lines, OVCAR-3 and CAOV-3, were treated by 120 μM resveratrol and their responses to the treatment and the statuses of Wnt, Notch and STAT3 signaling in them were analyzed by multiple experimental approaches. Selective inhibitors of Wnt, Notch or STAT3 signaling were employed to treat OVCAR-3 and CAOV-3 cells to elucidate the significance of individual signaling pathways for ovarian cancers.
  
  
  RESULTS
  The results demonstrated distinct inhibitory effects of resveratrol on human ovarian cancer cells in terms of remarkable G1 phase accumulation, increased apoptosis fraction and concurrent suppression of Wnt, Notch and STAT3 signaling as well as their downstream cancer-related gene expression. Treatments with Wnt, Notch or STAT3 selective inhibitor revealed that only AG490, a JAK-specific inhibitor, inhibits OVCAR-3 and CAOV-3 cells in the extent as similar as that of resveratrol.
  
  
  CONCLUSIONS
  Our results suggest the significance of STAT3 activation in the maintenance and survival of ovarian cancer cells. The activated STAT3 signaling is the critical molecular target of resveratrol. Resveratrol would be a promising candidate in the management of ovarian cancers, especially the ones with resistance to conventional therapeutic agents.
authors.affiliation: Department of Clinical Oncology, Second Affiliated Hospital of Dalian Medical University, Dalian, 110042, China. dlzlx2012@163.com.
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Zhong
authors.affiliation: Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, Dalian Medical University, Dalian, 116044, China. lihongmcn@dlmedu.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, Dalian Medical University, Dalian, 116044, China. moliwusx@sina.com.
authors.forename: Mo-Li
authors.initials: ML
authors.lastname: Wu
authors.affiliation: Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, Dalian Medical University, Dalian, 116044, China. christinaliu1979@163.com.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Liu
authors.affiliation: Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, Dalian Medical University, Dalian, 116044, China. 315zmj@163.com.
authors.forename: Ming-Jun
authors.initials: MJ
authors.lastname: Zhong
authors.affiliation: Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, Dalian Medical University, Dalian, 116044, China. chenxydl@163.com.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Chen
authors.affiliation: Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, Dalian Medical University, Dalian, 116044, China. jialiudl@aliyun.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Clinical Oncology, Second Affiliated Hospital of Dalian Medical University, Dalian, 110042, China. yangzhangdl@126.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation; D051880:Receptors, Notch / Q000096:biosynthesis; D000077185:Resveratrol; D050796:STAT3 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D013267:Stilbenes / Q000008:administration & dosage*; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D051880:Receptors, Notch; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013267:Stilbenes; D000077185:Resveratrol