Abstract
Obesity has been associated with both the carcinogenesis and poor prognosis of colon cancer, one of the leading causes of cancer-related death. Increased blood levels of insulin in obese subjects have been demonstrated to play a key role in carcinogenesis. It is also possible that insulin affects treatment efficacy, leading to poor prognosis. In this study, we demonstrated that insulin can increase HT29 colon cancer cell line resistance to cycloheximide and 5- fluorouracil induced cytotoxicity. This effect can be inhibited by the PI3K/Akt inhibitor Ly294002, indicating the important role of this pathway in the insulin-induced inefficacy of chemotherapy. The insulin-induced resistance to cycloheximide and 5-fluorouracil can be used in drug screening to overcome the inefficacy of chemotherapy in obesity-associated colon cancer.
Keywords: Insulin, PI3K/Akt pathway, cycloheximide, 5-fluorouracil, cytotoxicity, Ly294002, obesity, HT29 cells, colon cancer
Current Drug Discovery Technologies
Title: Insulin Decreases Therapeutic Efficacy in Colon Cancer Cell Line HT29 Via the Activation of the PI3K/Akt Pathway
Volume: 8 Issue: 2
Author(s): Jiezhong Chen, Andrew Katsifis, Changhua Hu and Xu-Feng Huang
Affiliation:
Keywords: Insulin, PI3K/Akt pathway, cycloheximide, 5-fluorouracil, cytotoxicity, Ly294002, obesity, HT29 cells, colon cancer
Abstract: Obesity has been associated with both the carcinogenesis and poor prognosis of colon cancer, one of the leading causes of cancer-related death. Increased blood levels of insulin in obese subjects have been demonstrated to play a key role in carcinogenesis. It is also possible that insulin affects treatment efficacy, leading to poor prognosis. In this study, we demonstrated that insulin can increase HT29 colon cancer cell line resistance to cycloheximide and 5- fluorouracil induced cytotoxicity. This effect can be inhibited by the PI3K/Akt inhibitor Ly294002, indicating the important role of this pathway in the insulin-induced inefficacy of chemotherapy. The insulin-induced resistance to cycloheximide and 5-fluorouracil can be used in drug screening to overcome the inefficacy of chemotherapy in obesity-associated colon cancer.
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Chen Jiezhong, Katsifis Andrew, Hu Changhua and Huang Xu-Feng, Insulin Decreases Therapeutic Efficacy in Colon Cancer Cell Line HT29 Via the Activation of the PI3K/Akt Pathway, Current Drug Discovery Technologies 2011; 8 (2) . https://dx.doi.org/10.2174/157016311795563820
DOI https://dx.doi.org/10.2174/157016311795563820 |
Print ISSN 1570-1638 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6220 |
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