title: PI3K/Akt/mTOR pathway dual inhibitor BEZ235 suppresses the stemness of colon cancer stem cells.
abstract: Colon cancer is one of the most common cancers worldwide with high mortality. A major issue in colon cancer treatment is drug-resistance and metastasis that have been ascribed to the cancer stem cells. In this study, colon cancer stem cells were isolated through sphere culture and verified with the cancer stem cell markers CD133, CD44, and CD24. It was demonstrated that the PI3K/Akt/mTOR signalling pathway was highly activated in the colon cancer stem cells and that inhibition of the PI3K/Akt/mTOR pathway by the inhibitor BEZ235 suppressed the colon cancer stem cell proliferation with reduced stemness indicated by CD133 and Lgr5 expressions. Treatment with insulin as a known activator of the PI3K/Akt pathway increased CD133 expression and decreased the effects of BEZ235 on colon cancer proliferation and survival. The data presented here collectively suggest that the PI3K/Akt/mTOR pathway underpins the stemness of colon cancer stem cells and BEZ235 is potentially a good drug candidate for treatment of colon cancer drug resistance and metastasis.
authors.affiliation: Australian Institute of Bioengineering and Nanotechnology, University of Queensland, St Lucia, Qld, Australia.|School of Biomedical Sciences, University of Queensland, St Lucia, Qld, Australia.
authors.forename: Jiezhong
authors.initials: J
authors.lastname: Chen
authors.affiliation: GeneCology Research Centre, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Maroochydore, Qld, Australia.
authors.forename: Renfu
authors.initials: R
authors.lastname: Shao
authors.affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezhi University, Xinjiang, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Australian Institute of Bioengineering and Nanotechnology, University of Queensland, St Lucia, Qld, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Monteiro
authors.affiliation: Aging Research Institute, Hangzhou Normal University, Hangzhou, Zhejiang, China.
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Liu
authors.affiliation: Australian Institute of Bioengineering and Nanotechnology, University of Queensland, St Lucia, Qld, Australia.
authors.forename: Zhi Ping
authors.initials: ZP
authors.lastname: Xu
authors.affiliation: Australian Institute of Bioengineering and Nanotechnology, University of Queensland, St Lucia, Qld, Australia.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Gu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007328:Insulin; D058539:Phosphatidylinositol 3-Kinase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D011804:Quinolines; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human; C531198:dactolisib
keywords: BEZ235; CD133; CD24; CD44; Lgr5; PI3K/Akt; cancer stem cells; colon cancer HCT-116; stemness