%0 Journal Article
%T Antitumor activities of ATP-competitive inhibitors of mTOR in colon cancer cells
%A Benjamin Blaser
%A Laurent Waselle
%A Anne Dormond-Meuwly
%A Marc Dufour
%A Didier Roulin
%A Nicolas Demartines
%A Olivier Dormond
%J BMC Cancer
%D 2012
%I BioMed Central
%R 10.1186/1471-2407-12-86
%X LS174T, SW480 and DLD-1 colon cancer cell lines were treated with PP242 an ATP-competitive inhibitor of mTOR, NVP-BEZ235, a dual PI3K/mTOR inhibitor or rapamycin. Tumor cell growth, proliferation and survival were assessed by MTS assay, 5-bromo-2'-deoxyuridine (BrDU) incorporation or by quantification of DNA fragmentation respectively. In vivo, the anticancer activity of mTOR inhibitors was evaluated on nude mice bearing colon cancer xenografts.PP242 and NVP-BEZ235 reduced the growth, proliferation and survival of LS174T and DLD-1 colon cancer cells more efficiently than rapamycin. Similarly, PP242 and NVP-BEZ235 also decreased significantly the proliferation and survival of SW480 cells which were resistant to the effects of rapamycin. In vivo, PP242 and NVP-BEZ235 reduced the growth of xenografts generated from LS174T and SW480 cells. Finally, we also observed that the efficacy of ATP-competitive inhibitors of mTOR was enhanced by U0126, a MEK inhibitor.Taken together, these results show that ATP-competitive inhibitors of mTOR are effective in blocking colon cancer cell growth in vitro and in vivo and thus represent a therapeutic option in colon cancer either alone or in combination with MEK inhibitors.Colorectal cancer (CRC) is one of the leading cause of cancer-related deaths worldwide [1]. Over the last decade, new therapeutic options for the treatment of CRC have been developed including targeted therapies. For example, drugs that block the vascular endothelial growth factor or the epidermal growth factor receptor have shown clinical activities and have been approved for the treatment of CRC [2]. However, despite these new treatments, the prognosis of CRC remains poor and new therapeutic strategies still need to be explored.The mammalian target of rapamycin (mTOR) is a serine/threonine kinase, present in two functionally distinct complexes mTORC1 and mTORC2. While mTORC1 is composed of mTOR, mLST8, raptor, deptor and PRAS40, mTORC2 consists of mTOR, rictor prot
%K Colon cancer
%K mTOR
%K Rapamycin
%K NVP-BEZ235
%K PP242
%K Proliferation
%K Xenograft
%U http://www.biomedcentral.com/1471-2407/12/86