PI3K/Akt/mTOR pathway dual inhibitor BEZ235 suppresses the stemness of colon cancer stem cells

Chen, Jiezhong, Shao, Renfu, Li, Feng, Monteiro, Michael, Liu, Jun-Ping, Xu, Zhi Ping and Gu, Wenyi (2015) PI3K/Akt/mTOR pathway dual inhibitor BEZ235 suppresses the stemness of colon cancer stem cells. Clinical and Experimental Pharmacology and Physiology, 42 12: 1317-1326. doi:10.1111/1440-1681.12493


Author Chen, Jiezhong
Shao, Renfu
Li, Feng
Monteiro, Michael
Liu, Jun-Ping
Xu, Zhi Ping
Gu, Wenyi
Title PI3K/Akt/mTOR pathway dual inhibitor BEZ235 suppresses the stemness of colon cancer stem cells
Journal name Clinical and Experimental Pharmacology and Physiology   Check publisher's open access policy
ISSN 1440-1681
Publication date 2015-12-01
Sub-type Article (original research)
DOI 10.1111/1440-1681.12493
Open Access Status Not Open Access
Volume 42
Issue 12
Start page 1317
End page 1326
Total pages 10
Place of publication Richmond, VIC, Australia
Publisher Wiley-Blackwell Publishing
Language eng
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.
Keyword BEZ235
Cancer stem cells
CD133
CD24
CD44
Colon cancer HCT-116
Lgr5
PI3K/Akt
Stemness
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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