Synergic effect between 5fluorouracil and celecoxib on hypoxic gastric cancer cells

Abstract

5fluorouracil (5FU) is commonly used in the treatment of gastric cancer; however, resistance to this drug occurs under hypoxic conditions. Celecoxib may be used to reverse this resistance. The aim of the present study was to elucidate the inhibitory effects and mechanisms of 5FU and celecoxib on the gastric cancer cell line SGC7901 under hypoxic conditions. SGC7901 cells were divided into four groups: Hypoxic control group, 5FU group, celecoxib group and 5FU/celecoxib combination group. Following treatment, the inhibition rates of cells were determined using an MTT assay. Protein and messenger RNA (mRNA) expression of hypoxiainducible factor 2α (HIF2α), adenosine triphosphatebinding cassette subfamily G member 2 (ABCG2) and octamer binding protein 4 (Oct4) were determined using immunohistochemistry, reverse transcription quantitative polymerase chain reaction (RTqPCR) and western blot analysis. The results demonstrated that the 5FU/celecoxib combination group had a significantly higher inhibition rate than the individually treated 5FU and celecoxib groups (P<0.05); inhibition rates were 66.09, 52.61 and 46.1%, respectively. mRNA and protein expression levels of HIF2α, ABCG2 and Oct4 were significantly lower in the celecoxib and 5FU/celecoxib combination groups (P<0.01) compared with those of the hypoxia control and 5FU groups. The 5FU group demonstrated the highest levels of the respective mRNA and proteins. In conclusion, the results of the present study indicated that celecoxib had antitumor effects, as it was shown to inhibit tumor cell growth via the inhibition of HIF2α, ABCG2 and Oct4. The 5FU/celecoxib combination had a synergic effect on tumor growth inhibition. This therefore suggested that inhibition of HIF2α, ABCG2 and Oct4 may be a potential method of reducing chemotherapy resistance and enhancing the effectiveness of chemotherapy treatment.