PI3K/Akt/mTOR Pathway Dual Inhibitor BEZ235 Suppresses the Stemness of Colon Cancer Stem Cells

Jiezhong Chen; Renfu Shao; Feng Li; Michael Monteiro; Jun-Ping Liu; Zhi Ping Xu; Wenyi Gu

doi:10.1111/1440-1681.12493

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PI3K/Akt/mTOR Pathway Dual Inhibitor BEZ235 Suppresses the Stemness of Colon Cancer Stem Cells

Journal article

Open access

Peer reviewed

PI3K/Akt/mTOR Pathway Dual Inhibitor BEZ235 Suppresses the Stemness of Colon Cancer Stem Cells

Jiezhong Chen, Renfu Shao, Feng Li, Michael Monteiro, Jun-Ping Liu, Zhi Ping Xu and Wenyi Gu

Clinical and Experimental Pharmacology and Physiology, Vol.42(12), pp.1317-1326

2015

DOI: https://doi.org/10.1111/1440-1681.12493

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Abstract

cancer stem cells

colon cancer HCT-11

BEZ235

PI3K/Akt

stemness

CD133

CD44

CD24

Lgr5

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, we isolated colon cancer stem cells through sphere culture and verified with the cancer stem cell markers CD133, CD44, and CD24. We 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. Our data collectively suggest that the PI3K/Akt/mTOR pathway underpins the stemness of colon cancer stem cells and BEZ235 is a good drug candidate potentially for treatment of colon cancer drug resistance and metastasis.

Details

Title: PI3K/Akt/mTOR Pathway Dual Inhibitor BEZ235 Suppresses the Stemness of Colon Cancer Stem Cells
Authors: Jiezhong Chen (Author) - University of Queensland
Renfu Shao (Author) - University of the Sunshine Coast - Faculty of Science, Health, Education and Engineering
Feng Li (Author) - Shihezi University, China
Michael Monteiro (Author) - University of Queensland
Jun-Ping Liu (Author) - Hangzhou Normal University, China
Zhi Ping Xu (Author) - University of Queensland
Wenyi Gu (Author) - University of Queensland
Publication details: Clinical and Experimental Pharmacology and Physiology, Vol.42(12), pp.1317-1326
Publisher: Wiley-Blackwell Publishing Asia
Date published: 2015
DOI: 10.1111/1440-1681.12493
ISSN: 0305-1870
Copyright note: Copyright © 2015 Wiley-Blackwell Publishing Asia. This is the accepted version of the following article: Chen, J., Shao, R., Li, F., Monteiro, M., Liu, J.-P., Xu, Z. P. and Gu, W. (2015), PI3K/Akt/mTOR pathway dual inhibitor BEZ235 suppresses the stemness of colon cancer stem cells. Clin Exp Pharmacol Physiol, 42: 1317-1326. doi:10.1111/1440-1681.12493, which has been published in final form at http://dx.doi.org/10.1111/1440-1681.12493
Organisation Unit: School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99449140902621
Output Type: Journal article

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