Abstract 4081: Sensitivity of gastric cancer cell lines against 2-deoxy-D-glucose is independent of PI3K/mTOR inhibition

2-deoxy-D-glucose (2-DG) is currently studied in Phase I clinical trials as a novel therapeutic strategy for anti-cancer therapy. Several preclinical studies have suggested that the anti-proliferative activity of 2-DG might be linked, amongst others, to the inhibition of the PI3K/mTOR signalling pathway. Blocking the PI3K/mTOR pathway has become a major focus for molecular targeted drug development. In the current study we assessed the biological relevance of PI3K/mTOR signalling for the anti-proliferative activity of 2-DG in gastric cancer cells. The gastric cancer cell lines (N87, MKN-28, MKN-45) were treated with 2-DG and evaluated for cell proliferation, apoptosis induction, cell cycle arrest, and PI3K/mTOR signalling. Everolimus, a specific mTORC1 inhibitor, was employed as positive control. Treatment with 2-DG potently suppressed cell proliferation resulting in an up to 300% reduced IC50 in the gastric cancer cell lines. Cell cycle inhibition and apoptosis induction varied substantially among cell lines. However, the distinct 2-DG sensitivity of gastric cancer cell lines was not reflected by any alteration in the PI3K/mTOR signalling pathway. In all cancer cell lines, no major inhibition of pERK and pAKT was observed, whereas both, 2-DG as well as everolimus strongly inhibited phosphorylation of S6. In contrast to 2-DG everolimus induced also a clear inhibition of 4EBP1 phosphorylation. In conclusion, inhibition of PI3K/mTOR signalling pathway by 2-DG differs from inhibition by everolimus and is not linked with 2-DG anti-proliferative sensitivity in gastric cancer cell lines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4081. doi:10.1158/1538-7445.AM2011-4081