地塞米松降低紫杉醇对肺癌细胞化疗作用的实验研究

The experimental research of dexamethasone reducing paclitaxel chemotherapy on lung cancer cells

目的研究地塞米松(dexamethasone,Dex)降低紫杉醇对肺癌细胞的化疗作用。方法 MTT法考察不同浓度的紫杉醇,以及地塞米松(10μmol·L^(-1))与不同浓度的紫杉醇联用,对肺癌细胞A549、Calu-1存活率的影响;流式细胞仪检测细胞周期;Western blot检测地塞米松对糖皮质激素受体(GR)、P-糖蛋白(P-gP)、多药耐药蛋白1(MRP-1)表达的影响;裸鼠移植瘤实验考察地塞米松降低紫杉醇对肺癌细胞的化疗作用。结果与紫杉醇单独作用相比,地塞米松(10μmol·L^(-1))联合紫杉醇降低了紫杉醇对肺癌细胞A549、Calu-1的敏感性,使IC_(50)明显提高(A549细胞:IC_(50)由0.58μmol·L^(-1)提高到1.35μmol·L^(-1);Calu-1细胞:IC_(50)由1.10μmol·L^(-1)提高到2.10μmol·L^(-1));地塞米松使GR蛋白表达增高,同时使P-gP、MRP-1蛋白的表达明显升高;地塞米松联合紫杉醇明显降低紫杉醇对裸鼠移植瘤的抑瘤效果。结论地塞米松联合紫杉醇可能使肺癌细胞产生耐药性,降低紫杉醇的化疗效果。

Aim To investigate the effect of dexamethasone on paclitaxel chemotherapy,when given before chemotherapy.Methods MTT method was used to investigate the effects of paclitaxel at different concentrations and dexamethasone(10μmol·L^-1)combined with paclitaxel at indicate dosages on the cell viability of lung cancer cells A549 and Calu-1.The cell cycle was detected by flow cytometry.The effect of dexamethasone on protein expression of glucocorticoid receptor(GR),P-glycoprotein(P-gP)and multidrug resistance protein-1(MRP-1)expression were detected by Western blot.The effect of dexamethasone on lung cancer resistance of paclitaxel xenografts in nude mice was studied as well.Results paclitaxel at indicate dosages with dexamethasone(10μmol·L^-1)showed significantly increased IC 50 value(A549:from 0.58 to 1.35μmol·L^-1;Calu-1 from 1.10 to 2.10μmol·L^-1).Dexamethasone activated GR,increased GR expression,and up-regulated the expression of P-gP and MRP-1.Dexamethasone combined with paclitaxel significantly decreased the antitumor effect of paclitaxel on nude mice transplanted tumor.Conclusions Giving dexamethasone before chemotherapy may cause resistance to cancer cells and reduce the effect of paclitaxel chemotherapy.