A: MC38 colon tumor-bearing mice were divided into 3 treatment groups: vehicle, rofecoxib (50 mg/l), or rofecoxib + HET0016 (5 mg·kg−1·day−1 ip). After 3 wk of treatment, plasma levels of 20-HETE, epoxyeicosatrienoic acids (EETs)/dihydroxyeicosatrienoic acids (DHETs), and other HETEs in tumor mice given different treatments were determined by LC/MS/MS. The levels of different eicosanoids were quantified by comparing the ratio of eicosanoids vs. 15(S)-HETE-d8. The plasma 20-HETE, 5-HETE, 8-HETE, 11-HETE, and 15-HETE levels were 2.84 ± 0.5, 10 ± 1.4, 4 ± 0.9, 5.23 ± 0.8, and 1.34 ± 0.5 ng/ml, respectively, in the vehicle-treated group. The EETs-to-DHETs ratio in the vehicle-treated group was 0.9 ± 0.2. Values are means ± SE; n = 4. *P < 0.05 vs. vehicle. #P < 0.05 vs. rofecoxib group. B: MC38 colon tumor-bearing mice were treated with HET0016 (5 mg·kg−1·day−1 ip) or vehicle for 3 wk. At the end of treatment, plasma PGs levels were determined by LC/MS/MS. Values are means ± SE. C: effects of 3-wk treatment of rofecoxib on Cyp4a expression in the liver and kidney of MC38 tumor mice. C, control; Rof, rofecoxib treatment.