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10.18632/oncotarget.12391

http://scihub22266oqcxt.onion/10.18632/oncotarget.12391
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suck abstract from ncbi


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pmid27705937
      Oncotarget 2016 ; 7 (51 ): 84190-84200
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  • Metformin potentiates anti-tumor effect of resveratrol on pancreatic cancer by down-regulation of VEGF-B signaling pathway #MMPMID27705937
  • Zhu M ; Zhang Q ; Wang X ; Kang L ; Yang Y ; Liu Y ; Yang L ; Li J ; Yang L ; Liu J ; Li Y ; Zu L ; Shen Y ; Qi Z
  • Oncotarget 2016[Dec]; 7 (51 ): 84190-84200 PMID27705937 show ga
  • Our previous study showed that resveratrol (RSV) exhibited not only anti-tumor effect, but also had potential tumor promotion effect on pancreatic cancer (Paca) cells through up-regulation of VEGF-B. We determined whether metformin (MET) could potentiate the anti-tumor effect of RSV on PaCa in this study. Combination of RSV (100 ?mol/l) and MET (20 mmol/l) significantly inhibited tumor growth and increased apoptosis of human PaCa in comparison with RSV or MET alone treatment in PaCa cell lines (Miapaca-2, Panc-1 and Capan-2). Combination of RSV (60 mg/kg, gavage) and MET (250 mg/kg, i.p.) significantly inhibited tumor growth in PaCa bearing nude mice (subcutaneous injection of 5 × 106 Miapaca-2 cells) in comparison with RSV or MET alone treatment on day 40. Combination treatment significantly decreased VEGF-B expression and inhibited activity of GSK-3? when compared to the RSV alone treatment. Up-regulated expressions of Bax, cleaved caspase-3 and down-regulated expression of Bcl-2 were observed in RSV+ MET group in comparison with RSV group either in vitro or in vivo. Inhibition of VEGF-B by VEGF-B small interfering RNA (siRNA) mimicked the effects of MET on PaCa cells. These results suggested that MET, a potential pharmacological inhibitor of VEGF-B signaling pathway, potentiated the anti-tumor effect of RSV on PaCa, and combination of MET and RSV would be a promising modality for clinical PaCa therapy.
  • |Animals [MESH]
  • |Antineoplastic Agents, Phytogenic/administration & dosage/pharmacology [MESH]
  • |Antineoplastic Combined Chemotherapy Protocols/*pharmacology [MESH]
  • |Apoptosis/drug effects [MESH]
  • |Cell Line, Tumor [MESH]
  • |Cell Survival/drug effects [MESH]
  • |Down-Regulation/drug effects [MESH]
  • |Drug Synergism [MESH]
  • |Humans [MESH]
  • |Hypoglycemic Agents/administration & dosage/pharmacology [MESH]
  • |Metformin/administration & dosage/*pharmacology [MESH]
  • |Mice, Nude [MESH]
  • |Pancreatic Neoplasms/*drug therapy/genetics/metabolism [MESH]
  • |RNA Interference [MESH]
  • |Resveratrol [MESH]
  • |Signal Transduction/drug effects [MESH]
  • |Stilbenes/administration & dosage/*pharmacology [MESH]
  • |Vascular Endothelial Growth Factor B/genetics/*metabolism [MESH]


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