| 童文娟，孙少卫.P-糖蛋白1对宫颈癌化疗耐药的影响及机制.[J].中南医学科学杂志.,2014,42(5):447-452. |
| P-糖蛋白1对宫颈癌化疗耐药的影响及机制 |
| P-glycoprotein 1 Mdiated the Resistance of Cervical Cancer to Etoposide |
| 投稿时间：2013-11-02 |
| DOI： |
| 中文关键词: P-糖蛋白1 宫颈癌 依托泊苷 Hela细胞 |
| 英文关键词:P-glycoprotein 1 cervical cancer etoposide Hela cells |
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| 中文摘要: |
| 目的探讨P-糖蛋白1（P-gP）在宫颈癌细胞对依托泊苷耐药中的作用机制。方法观察不同分期宫颈癌组织和慢性宫颈炎组织中P-gP的表达差异。取Hela细胞分别用azithromycin和cyclosporine A处理6 h后，再与依托泊苷孵育不同时间，高效液相色谱（HPLC）检测细胞内依托泊苷含量。将Hela细胞培养于培养皿或transwell小室中，用依托泊苷处理30 min，再分别与azithromycin和cyclosporine共孵育，检测transwell下室培养液中依托泊苷含量，同时检测各组细胞凋亡情况及凋亡相关因子Bcl-2和Bax的表达水平。结果P-gP在宫颈癌组织中表达显著高于宫颈炎组织。azithromycin可增强依托泊苷对Hela细胞的损伤作用，并呈浓度依赖性地上调Bax表达，降低Bcl-2水平，而cyclosporine A则对Hela细胞有保护作用。Transwell培养实验发现，azithromycin增加Hela细胞层对依托泊苷的通透性，而cyclosporine A则降低其通透性。结论P-gP促使Hela细胞泵出依托泊苷，减轻细胞损伤，因此介导了宫颈癌对依托泊苷的耐药性。 |
| 英文摘要: |
| ObjectiveTo investigate the roles of P-glycoprotein 1 on etoposide resistance of cervical cancer cells.MethodThe expression of P-glycoprotein 1 in cervical cancer and chronic cervicitis tissue were observed at different periods.The hela cells were treated with azithromycin (P-glycoprotein 1 activator) or cyclosporine A (P-glycoprotein 1 inhibitor) for 6 hours,then incubated with etoposide for different times.The content of etoposide in hela cells was detected by HPLC.Hela cells were grown on a Transwell insert to obtain a tight monolayer and preincubated with etoposide for 30 minutes,then incubated for another 12h after addition of azithromycin,or cyclosporine in the apical reservoir,HPLC was used to detect the content of etoposide in bottom reservoir.Hela cells were treated with azithromycin or cyclosporine for 24h after preincubated with etoposide,the cell viability was determined by MTT assay,Western blot was used to analyze the expression of apoptosis related proteins Bcl-2 and Bax.ResultsThe expression of P-glycoprotein 1 was significantly higher in cervical cancer tissues than in cervicitis,and its expression level was closely related with cancer staging.Azithromycin enhanced the cytotoxic effect of etoposide on hela cells,increased the expression of Bax,and decreased Bcl-2 in concentration-dependent manner,while cyclosporine A played a protective role on hela cells,up-regulated the expression of Bcl-2,and inhibited the expression of Bax.Transwell culture experiment showed that,azithromycin increased the permeability of HeLa cell layer to etoposide,but cyclosporine A prevented the passage of etoposide across cell layer.ConclusionP-glycoprotein 1 promoted HeLa cells to pump out etoposide,and relieved its cytotoxic effect,which therefore mediated the resistance of cervical cancer to etoposide. |
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