Insulin decreases therapeutic efficacy in colon cancer cell line HT29 via the activation of the PI3K/Akt pathway.

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.

• Authors: Jiezhong Chen, Andrew Katsifis, Changhua Hu, Xu-Feng Huang
• Journal: Current drug discovery technologies (Curr Drug Discov Technol) Vol. 8 Issue 2 Pg. 119-25 (Jun 2011) ISSN: 1875-6220 [Electronic] United Arab Emirates
• PMID: 21513489 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Chromones
• Insulin
• Morpholines
• Phosphoinositide-3 Kinase Inhibitors
• Protein Kinase Inhibitors
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Cycloheximide
• Oncogene Protein v-akt
• Fluorouracil

Topics

• Antineoplastic Agents (pharmacology)
• Cell Survival (drug effects)
• Chromones (pharmacology)
• Colonic Neoplasms (enzymology, etiology, pathology)
• Cycloheximide (pharmacology)
• Dose-Response Relationship, Drug
• Drug Resistance, Neoplasm
• Enzyme Activation
• Fluorouracil (pharmacology)
• HT29 Cells
• Humans
• Insulin (metabolism)
• Morpholines (pharmacology)
• Obesity (complications, enzymology)
• Oncogene Protein v-akt (antagonists & inhibitors, metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Phosphorylation
• Protein Kinase Inhibitors (pharmacology)
• Signal Transduction (drug effects)
• Time Factors