Metformin potentiates rapamycin and cisplatin in gastric cancer in mice

Oncotarget. 2015 May 20;6(14):12748-62. doi: 10.18632/oncotarget.3327.

Abstract

Here we showed that pAMPKα and PTEN were down-regulated and p-mTOR, p-S6, p-4EBP1, MMP7, and DCN1 were up-regulated in human gastric cancer tissue samples as compared to that in the noncancerous tissues. Metformin inhibited tumor growth in mice. Also it enhanced cisplatin- or rapamycin-induced reduction of tumor growth as compared with treatment of either drug alone. In addition to activation of AMPK and suppression of the mTOR pathway, a series of increased and decreased genes expression were induced by metformin, including PTEN, MMP7, and FN1. We suggest that metformin could potentially be used for the treatment of gastric cancer especially in combination with cisplatin or rapamycin.

Keywords: experimental therapy; gastric cancer; gene expression; metformin; mouse model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Blotting, Western
  • Cell Cycle / drug effects
  • Cisplatin / administration & dosage
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Male
  • Metformin / administration & dosage
  • Mice
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Sirolimus / administration & dosage
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Transcriptome / drug effects*
  • Xenograft Model Antitumor Assays

Substances

  • Metformin
  • Cisplatin
  • Sirolimus