The Effects Of Selected Cyclooxygenase-2 Inhibition Or Dual Cyclooxygenase-2/5-lipoxygenase Inhibition On The Proliferation Of Esophageal Squamous Cell Carcinoma Cells

AIMS: To investigate the effect and potential mechanism of NS-398, a selected COX-2 inhibitor and licofelone, a dual COX-2/5-LOX inhibitor on the proliferation of TE-1, an esophageal squamous cell carcinoma cell line.METHODS: TE-1 cells were divided into drug treatment group, blank control group and DMSO control group. Cells were treated by licofelone or NS-398 in 4 concentrations, including 25μM, 50μM, 75μM and 100μM.Cell proliferation were assessed by Cell Counting Kit-8 assay. Protein and messenger RNA (mRNA) expression of COX-2 and 5-LOX were determined by reverse transcriptase- polymerase chain reaction (RT-PCR) and Western blot, respectively. The concentrations of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were measured by ELISA Kit. Flow cytometer was used for the cell cycle measurement.RESULTS: Cell proliferation inhibition was found in both time- and concentration- dependent manners in TE-1 cells treated with licofelone, but not in those treated by NS-398. The cell growth inhibitions in NS-398 groups were found in cells treated under the concentration of 50μM for 24h and 25μM, 50μM and 100μM for 48h. (P<0.05),Time- and concentration-dependent inhibition of COX-2 mRNA and protein expression were found in TE-1 cells treated with either licofelone or NS-398, while the expression downregulation of 5-LOX mRNA and protein were found only in cells treated with licofelone. The level of PGE2 was inhibited in TE-1 cells treated by either NS-398 or licofelone in both time- and concentration- dependent manners (P<0.05), however, the inhibition of LTB4 level was found only in licofelone treated cells (P<0.05). The LTB4 levels were showed an upregulation tendency in cells treated with NS-398, but a significant difference was found only under the concentration of 100μM. After 24h treatment with 100μM of licofelone and 50μM of NS-398, the percentages of TE-1 cells in G0/G1-phase were 67.1% and 63.8%, respectively, while those in S-phase were 16.8% and 17.3%, respectively, which were significantly different from those in control groups (P<0.05).CONCLUSIONS: Those results implied that both COX-2 and 5-LOX played important roles in the proliferation regulation of esophageal squamous cell carcinoma. Selected COX-2 inhibition results in the promotion of cell proliferation in several specific concentrations when administrated alone, which may be due to the activation of LOX pathway. A dual COX-2/5-LOX inhibitor should be more effective for the inhibition of esophageal squamous cell carcinoma proliferation.