14,15-Epoxyeicosatrienoic acid induces the proliferation and anti- apoptosis of human carcinoma cell

BACKGROUND AND THE PURPOSE OF THE STUDY: Epoxyeicosatrienoic acids (EETs), which are cytochrome P450 epoxygenase metabolites of arachidonic acid, have anti-inflammatory effects, modulate smooth muscle proliferation, and inhibit smooth muscle migration. This study was designed to determine whether exogenous EETs have any effect on the cell proliferation and apoptosis of carcinoma cell as well as the possible signaling pathways of EETs in this regulation. METHODS: The effects of EETs on the proliferation and anti-apoptosis of human carcinoma cells were measured by MTT assay and flowcytometric analysis, and the regulation of PPARγ, epithelial growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK), phosphatidylinositol 3 (PI3)-Kinase/AKT pathways was investigated by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot analysis. RESULTS: Results of this study suggested that 14, 15-EET may activate the expression of PPARγ in Tca-8113 cells. 14,15-EET may stimulate cell proliferation, and increase the percentage of cells during S-G2-M phase in Tca-8113 cells significantly. The levels of EGFR, ERK, and PI3 kinase/AKT proteins were significantly induced by treatment of 14, 15-EET and 14,15-EET/AUDA, but no significant changes were observed by addition of GW9662. CONCLUSION: These findings suggest that exogenous 14,15-EET has potent inhibitory effect on proliferation, and could induce apoptosis in Tca-8113 cell, and these changes are related to the expression of PPARγ, the activation of EGFR, ERK, and PI3 kinase/AKT proteins.