[Promotive effects of epoxyeicosatrienoic acids (EETs) on proliferation of tumor cells].

BACKGROUND & OBJECTIVE: Epoxyeicosatrienoic acids (EETs) are generated from arachidomic acid by cytochrome P450(CYP). Previous studies revealed very strong and selective expression of CYP expoxygenase in human cancer tissues, but almost none in adjacent normal tissues. This study was to investigate the promotive effect of EETs on proliferation of tumor cells and the possible mechanisms.

METHODS

Four tumor cell lines, Tca-8113, A549, Ncl-H446 and HepG2, were treated with different concentrations of EETs (8,9-EET, 11,12-EET and 14,15-EET) for 12, 24, 48 and 72 h, respectively. Cell proliferation was measured using the MTT assay. The effect of exogenous EETs on cell cycle of Tca-8113 cells was assessed by flow cytometry. Signal transduction inhibitors of PI3K (LY294002), MAPKK (PD98059), MAPK (apigenin) and PKC (H7) were used to block EETs-induced cell proliferation. Expressions of the total protein and phosphorylated ERK1/2 and Akt were determined by Western blot.

RESULTS

EETs promoted proliferation of tumor cells compared with the control and vehicle group in a dose-and time-dependent manner (P<0.01). Incubation of tumor cells with EETs markedly increased the cell number at S/G2-M phase. The percentages of Tca-8113 cells at S and G2-M phases were (49.7+/-7.5%) vs. (17.2+/-9.7%) (P<0.01) and (21.0+/-5.3%) vs. (4.9+/-7.3%), respectively(P<0.01) with and without the treatment of 11,12-EET. EETs incubation significantly enhanced phosphorylation of MARK as well as PI3K/Akt in tumor cells. LY294002, PD98059, apigenine and H7 reduced the stimulative effect of EETs on cell proliferation.

CONCLUSION

EETs possess the promotive effect on proliferation of tumor cells via activation of MAPK and PI3K/Akt signal pathways.