title: Resveratrol inhibits ovarian tumor growth in an in vivo mouse model.
abstract: BACKGROUND
  Resveratrol inhibits the growth of ovarian carcinoma cells in vitro through the inhibition of glucose metabolism and the induction of both autophagy and apoptosis. In the current study, we investigated the metabolic and therapeutic effects of resveratrol in vivo.
  
  
  METHODS
  A fluorescent xenograft mouse model of ovarian cancer was used. Mice were treated with cisplatin, resveratrol, or vehicle alone. Tumor burden was assessed using whole-body imaging. The effect of resveratrol on glucose uptake in vivo was determined using micro-positron emission tomography scanning. To determine whether resveratrol could inhibit tumor regrowth, tumor-bearing mice were treated with cisplatin followed by either daily resveratrol or vehicle. Autophagic response in resected tumors taken from mice treated with resveratrol was examined by transmission electron microscopy. Glycolysis and mitochondrial respiration in ovarian tumor cells after treatment with resveratrol was assessed.
  
  
  RESULTS
  Mice treated with resveratrol and cisplatin were found to have a significantly reduced tumor burden compared with control animals (P<.001). Resveratrol-treated mice demonstrated a marked decrease in tumor uptake of glucose compared with controls. After treatment with cisplatin, "maintenance" resveratrol resulted in the suppression of tumor regrowth compared with mice receiving vehicle alone (P<.01). Tumors resected from mice treated with resveratrol exhibited autophagosomes consistent with the induction of autophagy. Treatment with resveratrol inhibited glycolytic response in ovarian tumor cells with high baseline glycolytic rates.
  
  
  CONCLUSIONS
  Treatment with resveratrol inhibits glucose uptake and has a significant antineoplastic effect in a preclinical mouse model of ovarian cancer. Resveratrol treatment suppresses tumor regrowth after therapy with cisplatin, suggesting that this agent has the potential to prolong disease-free survival. Cancer 2016;122:722-729. © 2015 American Cancer Society.
authors.affiliation: Department of Obstetrics and Gynecology, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Lijun
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Obstetrics and Gynecology, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Weimin
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Gong
authors.initials: G
authors.lastname: He
authors.affiliation: Department of Biostatistics, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Rork D
authors.initials: RD
authors.lastname: Kuick
authors.affiliation: Department of Obstetrics and Gynecology, St. Luke's-Roosevelt Hospital, New York, New York.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Gossner
authors.affiliation: Department of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, Connecticut.
authors.forename: Angela S
authors.initials: AS
authors.lastname: Kueck
authors.affiliation: Department of Obstetrics and Gynecology, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Heather
authors.initials: H
authors.lastname: Wahl
authors.affiliation: Department of Obstetrics and Gynecology, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Opipari
authors.affiliation: Department of Obstetrics and Gynecology, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: J Rebecca
authors.initials: JR
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D000077216:Carcinoma, Ovarian Epithelial; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D009368:Neoplasm Transplantation; D009375:Neoplasms, Glandular and Epithelial / Q000000981:diagnostic imaging* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D005947:Glucose; D002945:Cisplatin; D000077185:Resveratrol
keywords: apoptosis; autophagy; glycolysis; ovarian cancer; resveratrol; tumor metabolism