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目的探讨三苯氧胺(TAM)对过表达乳腺癌耐药蛋白(BCRP)的JAR/VP16细胞的逆转耐药作用。方法在人绒癌细胞株JAR和对VP16耐药的JAR/VP16细胞株中以MTT法比较单药VP16组、TAM组及两药联合组的药物毒性,并运用流式细胞术以hochest33342和PI双染观察两株细胞在加与不加TAM时的胞内荧光值强度。以RT-PCR和Western blot方法在 mRNA水平和蛋白水平观察TAM、VP16及两药联用时BCRP表达水平。结果JAR/VP16细胞株与JAR细胞相比,BCRP的表达量上调;TAM能显著增加VP16的抗肿瘤作用,与VP16单药组相比,联合用药组的细胞抑制率增加(P<0.05);TAM可下调BCRP的表达。结论BCRP的过表达可能导致了JAR/VP16细胞对VP16的耐药,而TAM可通过下调BCRP的表达及抑制BCRP的功能,从而逆转这种耐药。
Objective To investigate the reversal drug resistance of tamoxifen (TAM) to JAR / VP16 cells overexpressing breast cancer resistance protein (BCRP). Methods MTT assay was used to compare the drug toxicity of single drug VP16 group, TAM group and two drug combination groups in human choriocarcinoma cell line JAR and VP16-resistant JAR / VP16 cell line, and using flowcytometry with hochest33342 and PI Double staining was used to observe the intracellular fluorescence intensity of two cells with and without TAM. The expression of BCRP was detected by RT-PCR and Western blot at mRNA and protein levels. Results The expression of BCRP was up - regulated in JAR / VP16 cells compared with that of JAR cells. TAM could significantly increase the antitumor effect of VP16. Compared with VP16 single - agent group, the cell inhibition rate of combination group increased (P <0.05). TAM can down-regulate BCRP expression. Conclusion Overexpression of BCRP may result in the resistance of JAR / VP16 cells to VP16. However, TAM can reverse this resistance by down-regulating the expression of BCRP and inhibiting the function of BCRP.