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目的:观察选择性环氧化酶-2(COX-2)抑制剂塞来昔布对口腔癌耐长春新碱细胞株KB/VCR细胞增殖的影响及对P-糖蛋白(P-gp)表达的影响。方法:将KB/VCR细胞分为长春新碱组、塞来昔布组、长春新碱联合塞来昔布用药组及对照组,采用MTT法检测对KB/VCR细胞的生长抑制作用,蛋白质印迹法检测P-gp蛋白的表达,流式细胞术检测细胞内Rho123的蓄积。结果:长春新碱与塞来昔布联合用药组对细胞生长抑制作用明显高于长春新碱组和塞来昔布组(P均<0.01)。长春新碱与塞来昔布联合用药组及塞来昔布组细胞的P-gp表达水平显著低于长春新碱组和对照组。长春新碱与塞来昔布联合用药组及塞来昔布组细胞内Rho123的荧光强度显著高于长春新碱组和对照组。结论:COX-2抑制剂塞来昔布可显著增强KB/VCR细胞对长春新碱的敏感性,其作用机制可能与下调P-gp的表达,增加细胞内长春新碱的蓄积有关。
Objective: To observe the effect of selective cyclooxygenase-2 (COX-2) inhibitor celecoxib on the proliferation of vincristine-resistant cell line KB / VCR and the expression of P-glycoprotein Impact. Methods: KB / VCR cells were divided into vincristine group, celecoxib group, vincristine combined with celecoxib group and control group. The growth inhibition of KB / VCR cells was detected by MTT assay. Western blotting Method to detect the expression of P-gp protein, flow cytometry to detect the accumulation of intracellular Rho123. Results: The combination of vincristine and celecoxib inhibited the growth of cells significantly compared with vincristine and celecoxib groups (all P <0.01). P-gp expression of vincristine and celecoxib combination group and celecoxib group was significantly lower than that of vincristine and control group. Fluorescence intensity of intracellular Rho123 in vincristine and celecoxib combination group and celecoxib group was significantly higher than that of vincristine and control group. CONCLUSION: Celecoxib, a COX-2 inhibitor, can significantly enhance the sensitivity of KB / VCR cells to vincristine. The mechanism may be related to the down-regulation of P-gp expression and the increase of intracellular accumulation of vincristine.