【摘要】 目的检测 P-糖蛋白(gp)底物化疗药物对多药耐药乳腺癌细胞侵袭转移相关基因基质金属蛋白酶2和9及其诱导物 CD147表达的影响和意义。方法选取耐阿霉素的 MCF 乳腺癌细胞系(MCF7/AdrR)及人乳腺癌细胞系 MCF7,在细胞培养过程是分别加入不同剂量的 P-gp 底物化疗药物紫杉醇和长春新碱以及非 P-gp 底物化疗药物博莱霉素,荧光实时定量 PCR 法检测基质金属蛋白酶2和9及其诱导物 CD147 mRNA 水平的变化;Western blot 法检测基质金属蛋白酶2和9及CD147蛋白水平的改变。结果加入博莱霉素后,无论 MCF7还是 MCF7/AdrR 细胞的上述各项检测指标均没有显著改变(P>0.05);加入紫杉醇和长春新碱后,MCF7/AdrR 细胞基质金属蛋白酶2和9及其诱导物 CD147在 mRNA 和蛋白水平上有显著上调(P<0.05),而 MCF7细胞则没有相应的改变(P>0.05)。结论作为 P-gp 底物的化疗药物可以上调阿霉素的 MCF 乳腺癌细胞基质金属蛋白酶2和9及其诱导物 CD147的表达,从而增强癌细胞侵袭转移的能力。更多还原

【Abstract】 Objective To investigate effects of P-glycoprotein(gp)substrate drugs on the expression of CD147 and MMP2 and 9 in multidrug resistant breast cancer cells.Methods MDR human breast cancer cell line,MCFT/AdrR,and its sensitive parental line,MCFT,were treated with various concentrations of P-gp substrate drugs,including paelitoxel and vincristine,and P-gp nonsubstrate drugs, bleomycin,in serum-free media.At the end of the treatment,expressions of CD147 and MMP2 and 9 were determined by real-time PCR and western blot.Results Increased expressions of CD147 and MMP2 and 9 were observed in multidrug resistant cancer cells compared with their parental MCF7 cells.After treatment with bleomycin,the expression of CD147 and MMP2 and 9 in both MCF7 and MCF7/AdrR cells remained unchanged(P>0.05).However,treatment with paclitoxel and vincristine resulted in a remarkable over- expression of CD147 and MMP2 and 9 at both transcription and protein levels in MCF7/AdrR cell line(P< 0.05),while MCF7 cells failed to show similar response.Conclusions P-gp substrate drugs can greatly upregulate the expression of CD147 and MMP2 and 9 in muhidrug resistant breast cancer cells,therefore enhancing the tumor metastatic capability.更多还原