Conjugated Linoleic Acid Downregulates Insulin-Like Growth Factor-I Receptor Levels in HT-29 Human Colon Cancer Cells

摘要: Conjugated linoleic acid (CLA) has chemoprotective properties in a variety of experimental cancer models. We have previously observed that dietary CLA inhibits colon tumorigenesis induced by 1,2-dimethylhydrazine rats. In addition, our vitro studies shown DNA synthesis and induces apoptosis HT-29 cells, the human adenocarcinoma cell line. The insulin-like growth factor (IGF) system regulates cells an autocrine mechanism. present study examined whether inhibitory effect is related to changes IGF cells. To determine IGF-II production, were incubated serum-free medium presence various concentrations CLA. decreased protein levels both mature pro transcripts. Whereas exogenous IGF-I produced increase number, neither nor counteracted negative regulatory Reverse transcriptase-polymerase chain reaction Western blot analysis total lysates revealed receptor (IGF-IR) transcript dose-dependent manner. Immunoprecipitation/Western inhibited IGF-I-induced phosphorylation IGF-IR insulin-receptor substrate (IRS)-1, recruitment p85 subunit phosphatidylinositol 3-kinase (PI3K) IGF-IR, IGF-IR-associated PI3K activity, phosphorylated Akt extracellular signal-regulated kinase (ERK)-1/2 levels. conclusion, inhibition proliferation induction may be mediated part its ability decrease downregulate signaling P13K/Akt ERK-1/2 pathways.