PI3K/Akt/mTOR pathway dual inhibitor BEZ235 suppresses the stemness of colon cancer stem cells
© 2015 Wiley Publishing Asia Pty Ltd. 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...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
| Published: |
Wiley-Blackwell Publishing Asia
2015
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| Online Access: | http://hdl.handle.net/20.500.11937/72938 |
| _version_ | 1848762881588330496 |
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| author | Chen, J. Shao, R. Li, F. Monteiro, M. Liu, Jian Xu, Z. Gu, W. |
| author_facet | Chen, J. Shao, R. Li, F. Monteiro, M. Liu, Jian Xu, Z. Gu, W. |
| author_sort | Chen, J. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2015 Wiley Publishing Asia Pty Ltd. 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. |
| first_indexed | 2025-11-14T10:54:37Z |
| format | Journal Article |
| id | curtin-20.500.11937-72938 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:54:37Z |
| publishDate | 2015 |
| publisher | Wiley-Blackwell Publishing Asia |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-729382018-12-13T09:33:39Z PI3K/Akt/mTOR pathway dual inhibitor BEZ235 suppresses the stemness of colon cancer stem cells Chen, J. Shao, R. Li, F. Monteiro, M. Liu, Jian Xu, Z. Gu, W. © 2015 Wiley Publishing Asia Pty Ltd. 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. 2015 Journal Article http://hdl.handle.net/20.500.11937/72938 10.1111/1440-1681.12493 Wiley-Blackwell Publishing Asia restricted |
| spellingShingle | Chen, J. Shao, R. Li, F. Monteiro, M. Liu, Jian Xu, Z. Gu, W. PI3K/Akt/mTOR pathway dual inhibitor BEZ235 suppresses the stemness of colon cancer stem cells |
| title | PI3K/Akt/mTOR pathway dual inhibitor BEZ235 suppresses the stemness of colon cancer stem cells |
| title_full | PI3K/Akt/mTOR pathway dual inhibitor BEZ235 suppresses the stemness of colon cancer stem cells |
| title_fullStr | PI3K/Akt/mTOR pathway dual inhibitor BEZ235 suppresses the stemness of colon cancer stem cells |
| title_full_unstemmed | PI3K/Akt/mTOR pathway dual inhibitor BEZ235 suppresses the stemness of colon cancer stem cells |
| title_short | PI3K/Akt/mTOR pathway dual inhibitor BEZ235 suppresses the stemness of colon cancer stem cells |
| title_sort | pi3k/akt/mtor pathway dual inhibitor bez235 suppresses the stemness of colon cancer stem cells |
| url | http://hdl.handle.net/20.500.11937/72938 |