肺癌耐药发生和细胞周期改变的流式细胞术分析

目的　探讨肺癌耐药发生过程中多药耐药相关蛋白 (multidrugresistance associatedprotein ,MRP)、P 糖蛋白表达和细胞周期改变的关系。方法　采用低浓度阿霉素 (ADM)诱导人肺腺癌GLC 82细胞系 ,通过流式细胞术双参数标记检测MRP、P 糖蛋白表达和细胞周期的变化。结果　低浓度可明显降低GLC 82肺癌细胞系细胞周期中G1期比例 ,增加S期比例 ;P 糖蛋白表达极弱 ,MRP表达率明显增加 ,呈时间依赖性 ,其表达与细胞周期中S期比例变化呈正相关 (r =0 .87,P =0 .0 0 0 1)。结论　MRP表达可能是肺癌细胞耐药发生的重要参与机制 ,其表达与细胞周期中S期的变化相关。

Development of drug resistance and alteration of cell cycle in lung cancer: a flow cytometric study

OBJECTIVE: To study the relationship between the expression of multidrug resistance-associated protein (MRP) and P-glycoprotein (P-gp) and alteration of cell cycle during the process of drug resistance in lung cancer. METHODS: Lung adenocarcinoma cell line GLC-82 was treated with low concentration of adriamycin. At 0, 24, 48, 72 and 96 hr following adriamycin treatment, the expression of MRP and P-gp, and cell cycle were examined by bi-parameter flow cytometry. RESULTS: Treatment of GLC-82 cells with adriamycin at a final concentration of 0.05 microgram/ml resulted in progressive decrease in cells in G1 phase and increase in cells in S phase of the cell cycle. The expression level of P-gp was very low and showed little change with time. In contrast, MRP expression was significantly increased in a time-dependent manner, and was positively correlated with changes in S phase of the cell cycle. CONCLUSION: MRP expression may play a major role in the development of resistance to adriamycin.