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

Metformin inhibits the growth of human pancreatic cancer xenografts.

Author information

1
Department of Medicine, Digestive Diseases Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.

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.

PMID:
23462329
PMCID:
PMC3681894
DOI:
10.1097/MPA.0b013e31827aec40
[Indexed for MEDLINE]
Free PMC Article

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