title: Resveratrol plays dual roles in pancreatic cancer cells.
abstract: OBJECTIVE
  Although the potential anticancer effect of resveratrol (RSV) on pancreatic cancer has been reported, its mechanism was not fully understood. The role of vascular endothelial growth factor B (VEGF-B) in cancer remains controversial. Herein, we aimed to examine whether the anticancer effect of RSV was related to the VEGF-B.
  
  
  METHODS
  The effect of RSV on pancreatic cancer cell line (capan-2 cells) was evaluated by CCK-8 assay, Hoechst 33342 staining, and flow cytometry. The mRNA level of VEGF-B was measured by real-time PCR. VEGF-B expression was knockdown by small interfering RNA (siRNA).The protein levels of VEGF-B, glycogen synthase kinase-3 beta (GSK-3β), and Bax were measured by Western blot.
  
  
  RESULTS
  Resveratrol treatment inhibited tumor growth, induced apoptosis, and up-regulated Bax expression in capan-2 cells. The mRNA and protein levels of VEGF-B were up-regulated after RSV treatment. However, VEGF-B siRNA treatment increased the apoptotic rate, and inhibited tumor activator GSK-3β, while Bax expression was not affected. The combination of RSV and VEGF-B siRNA showed significantly higher apoptotic rate in comparison with RSV or VEGF-B siRNA mono-treatment group.
  
  
  CONCLUSIONS
  Resveratrol plays dual roles in pancreatic cancer: as a tumor suppressor via the up-regulation of Bax; as a tumor activator via the up-regulation of VEGF-B; and the anticancer effect of RSV is much stronger than the cancer promotion effect. The combination of RSV with pharmacological inhibitor of VEGF-B might, therefore, be a promising modality for clinical pancreatic cancer therapy.
authors.affiliation: Department of Histology and Embryology, Nankai University School of Medicine, 94 Weijin Road, Nankai District, Tianjin, 300071, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.forename: Wencong
authors.initials: W
authors.lastname: Tian
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yinan
authors.initials: Y
authors.lastname: Yang
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhang
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Liu
authors.forename: Yanna
authors.initials: Y
authors.lastname: Shen
authors.forename: Zhi
authors.initials: Z
authors.lastname: Qi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D034741:RNA, Small Interfering; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D042561:Vascular Endothelial Growth Factor B / Q000096:biosynthesis* / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: C494826:BAX protein, human; D034741:RNA, Small Interfering; D013267:Stilbenes; C467485:VEGFB protein, human; D042561:Vascular Endothelial Growth Factor B; D051028:bcl-2-Associated X Protein; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D000077185:Resveratrol