Metformin inhibits the growth of human pancreatic cancer xenografts

Pancreas. 2013 Jul;42(5):781-5. doi: 10.1097/MPA.0b013e31827aec40.

Abstract

Objective: Pancreatic ductal adenocarcinoma is a devastating disease, with an overall 5-year survival rate of only 3% to 5%. As the current therapies offer very limited survival benefits, novel therapeutic strategies are urgently required to treat this disease. Here, we determined whether metformin administration inhibits the growth of PANC-1 and MiaPaCa-2 tumor xenografts in vivo.

Methods: Different xenograft models, including orthotopic implantation, were used to determine whether intraperitoneal or oral administration of metformin inhibits the growth of pancreatic cancer in vivo.

Results: We demonstrate that metformin given once daily intraperitoneally at various doses (50-250 mg/kg) to nude mice inhibited the growth of PANC-1 xenografts in a dose-dependent manner. A significant effect of metformin was obtained at 50 mg/kg and maximal effect at 200 mg/kg. Metformin administration also caused a significant reduction in the phosphorylation of ribosomal S6 protein and ERK in these xenografts. Metformin also inhibited the growth of pancreatic cancer xenografts when administered orally (2.5 mg/mL) either before or after tumor implantation. Importantly, oral administration of metformin also inhibited the growth of MiaPaCa-2 tumors xenografted orthotopically.

Conclusions: The studies presented here provide further evidence indicating that metformin offers a potential novel approach for pancreatic ductal adenocarcinoma prevention and therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Blotting, Western
  • Body Weight / drug effects
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacology
  • Injections, Intraperitoneal
  • Male
  • Metformin / administration & dosage
  • Metformin / pharmacology*
  • Mice
  • Mice, Nude
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Phosphorylation / drug effects
  • Ribosomal Protein S6 Kinases / metabolism
  • Time Factors
  • Tumor Burden / drug effects*
  • Xenograft Model Antitumor Assays*

Substances

  • Hypoglycemic Agents
  • Metformin
  • Ribosomal Protein S6 Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3