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目的:研究防己诺林碱对紫杉醇在MDR1-MDCKⅡ细胞跨膜转运的调控作用。方法:以外排转运蛋白P-gp底物紫杉醇为模型药物,盐酸维拉帕米为对照,考察防己诺林碱调控紫杉醇在MDR1-MDCKⅡ细胞模型的跨膜转运作用。采用RP-HPLC检测紫杉醇在转运介质中的药物浓度,计算其表观渗透系数。结果:紫杉醇在P-gp高表达的MDR1-MDCKⅡ细胞模型中外排的速率明显快于吸收的速率。与紫杉醇单用相比,紫杉醇分别联用盐酸维拉帕米及防己诺林碱后,紫杉醇吸收速率均显著增加,而外排速率均显著降低,相同浓度的防己诺林碱抑制转运作用强于对照盐酸维拉帕米。结论:防己诺林碱能够明显降低紫杉醇在MDR1-MDCKⅡ细胞的外排作用,抑制由P-gp介导的多药耐药。
OBJECTIVE: To study the regulatory effect of anti-tubulin on the transmembrane transport of paclitaxel in MDR1-MDCKII cells. METHODS: Paclitaxel (P-gp), a substrate for transporter transporter P-gp, was used as a model drug and verapamil hydrochloride as a control. The concentration of paclitaxel in the transport medium was determined by RP-HPLC, and the apparent permeability coefficient was calculated. RESULTS: The rate of efflux of paclitaxel in MDR1-MDCKII cell model with high P-gp expression was significantly faster than that of the absorption rate. Compared with paclitaxel alone, paclitaxel combined with verapamil hydrochloride and anti-tubulin, respectively, the paclitaxel absorption rate were significantly increased, while the efflux rate was significantly reduced, the same concentration of anti-tetindrine inhibited transport stronger than Control verapamil hydrochloride. CONCLUSION: The anti-tubulin can significantly reduce the efflux of paclitaxel in MDR1-MDCKII cells and inhibit the multi-drug resistance mediated by P-gp.