Insulin caused drug resistance to oxaliplatin in colon cancer cell line HT29

J Gastrointest Oncol. 2011 Mar;2(1):27-33. doi: 10.3978/j.issn.2078-6891.2010.028.


Introduction: Obesity is associated with poor prognosis of colon cancer and the mechanism for this is unknown. This study tested insulin-caused resistance to oxaliplatin via activation of PI3K/Akt pathway in HT29 cells.

Methods: The effect of insulin on oxaliplatin cytotoxicity was tested by pre-incubation with 1µM insulin followed by addition of oxaliplatin. Phosphorylated Akt was determined by Western blotting.

Results: Addition of 1µM insulin decreased the cytotoxicity of oxaliplatin. PI3K specific inhibitor Ly294002 abolished such an effect of insulin. pAkt were highly activated by insulin plus oxaliplatin and inhibited by addition of Ly294002.

Conclusion: Insulin decreased drug efficacy of oxaliplatin in HT29 cells, which could be mediated by the activation of the PI3K/Akt pathway.

Keywords: HT29 cell; Insulin; Obesity; PI3K/Akt pathway; colon cancer.