LY294002逆转KB/VCR细胞多药耐药的作用及机制

目的 探讨蛋白激酶抑制剂LY294002对多药耐药细胞KB/VCR的耐药逆转作用及逆转机制.方法 采用MTT法检测LY294002对VCR和ADR的耐药逆转作用,流式细胞仪检测Rh123在KB和KB/VCR细胞内的蓄积,Western blot法检测LY294002对P-gp蛋白表达的影响,DAPI染色检测细胞凋亡.结果 LY294002对化疗药物具有协同增效作用,可以显著逆转KB/VCR的耐药性,能明显减少Rh123的外排,同时降低P-gp的表达.结论 LY294002能够逆转KB/VCR细胞的多药耐药性,不仅能够抑制P-gp功能,而且能够降低P-gp蛋白表达,使肿瘤细胞内化疗药物的浓度增加,提高化疗药物的杀伤作用.

Reversal effect of LY294002 on multidrug resistance of KB/VCR cells

Objective To explore the reversal effect and potential mechanism of protein kinase inhibitor LY294002 on muhidrug resistance of KB/VCR cells. Methods MTF assay was used to investigate reversal effect of LY294002 on mul- tidrug resistance of VCR and ADR. Flow cytometry was used to measure Rh123 accumulation in KB and KB/VCR cells. Western blotting was used to detect the effect of LY294002 on protein expression of P-gp. DAPI staining was used to ana- lyze the apoptosis of KB/VCR cells. Results LY294002 obviously reversed the muhidrug resistant phenotype of KB/VCR cells. Further study showed that it significantly increased the accumulation of Rh123 in KB/VCR cells, and LY294002 also down-regulated the expression of P-gp. Conclusion LY294002 may reverse the multidrug resistance of KB/VCR cells, not only can inhibit P-gp function, but also can down-regulate the expression of P-gp protein, increase the concentration of chemotherapy drugs in tumor cells, and improve the killing effect of chemotherapy.