Abstract: AIM: To observe the mechanism of celecoxib reversal adriamycin resistance in NK/T cell lymphoma cells.  METHODS: SNK6 and SNK6/ADR cells were treated with celecoxib of different concentrations (10, 20, 40, 60, 80, 100 μmol/L), the growth inhibition rate of SNK6 and SNK6/ADR were measured by MTT method. The IC50 and low-toxic concentration of celecoxib on SNK6/ADR cells were calculated, then SNK6/ADR cells were treated with low-toxic concentration of celecoxib combined with adriamycin, the IC50 and reverse times were calculated. The apoptosis of SNK6/ADR cells were detected by FMC. The effects of apatinib on the accumulation of rhodamine 123 in SNK6/ADR cells were investigated by flow cytometry. The mRNA expressions of Notch 1, NF-κB and STAT3 were detected by RT-PCR. The protein expressions of Notch 1, NF-κB, STAT3, P-gp were detected by Western blot. RESULTS: Different concentrations of celecoxib can significantly inhibit the proliferation of SNK6 and SNK6/ADR cells. The inhibition increased with the increase of celecoxib concentration. The IC50 of celecoxib on SNK6 and SNK6/ADR cells were (57.54±6.89) μg/mL, (43.39±4.38) μg/mL, The IC50 of adriamycin on SNK6/ADR cells was (7.34±0.56) μg/mL. After adriamycin combined with celecoxib 10 μmol/L treat SNK6/ADR cells, the IC50 on SNK6/ADR cells was (3.51±0.25) μg/mL (P<0.01), and the reverse times was 2.09. After adriamycin combined with celecoxib, compared with the adriamycin group, the apoptosis rate of SNK6/ADR cells was significantly increased (P<0.01). The intracellular accumulation of rhodamine 123 was significantly increased (P<0.01). The protein expressions of P-gp was significantly decreased (P<0.01). The mRNA and protein expressions of Notch 1, NF-κB, STAT3 were significantly decreased (P<0.01). CONCLUSION: Celecoxib can induce apoptosis and reverse adriamycin resistance in NK/T cell lymphoma cells, the mechanism may be regulating the Notch 1/NF-κB/STAT3 signaling pathway.

Key words: celecoxib, NK/T cell lymphoma cells, adriamycin resistance, Notch 1/NF-κB/STAT3