超声破坏LHRHa靶向脂质微泡造影剂对卵巢癌A2780/DDP细胞内顺铂浓度的影响  

Effect of ultrasound mediated LHRHa Carrying microbubbles destruction on the concentration of Cisplatin(DDP) in ovarian cancer cell A2780/DDP

作　　者：严宇[1] 孙江川[1] 常淑芳[1] 郭娟[1] 朱轶[1] 李敏[1] 朱深银[2] 王志刚[1] 

机构地区：[1]重庆医科大学附属第二医院妇产科,重庆400010 [2]重庆医科大学附属第一医院药剂科,重庆400016

出　　处：《激光杂志》2011年第3期50-52,共3页Laser Journal

基　　金：国家自然科学基金(编号;30801228);重庆市自然科学基金(编号:CSTC;2008BB5405);重庆市卫生局项目(编号:07-2-098)资助

摘　　要：目的:探讨超声联合LHRHa靶向脂质微泡对卵巢癌耐药细胞内化疗药物DDP浓度的影响。方法:取对数生长期的A2780/DDP细胞,分为空白组,DDP组,DDP+超声组,DDP+超声+普通脂质微泡以及DDP+超声+LHRHa靶向脂质微泡组等5组,分别给予不同的干预手段,分别于作用后12小时、24小时、48小时撤药,采用高效液相色谱法(HPLC)法测定各组细胞中DDP的浓度,流式细胞仪检测脂质微泡加超声处理后的不同时间点(即时、12小时、24小时、48小时)细胞膜对PI染料的通透性。结果:超声联合脂质微泡可增加细胞膜对PI染料的通透性,这种作用在处理后即刻最明显,随着时间的延长,细胞膜对PI染料的通透性逐渐下降。在所建立的色谱条例下,测得DDP浓度呈良好线性关系,相关系数为R=0.9994。经HPLC测定DDP在各组细胞中的浓度结果显示:DDP+超声+LHRHa靶向脂质微泡组在处理后12小时、24小时胞内药物浓度明显高于其他组(p<0.05)。结论:超声联合LHRHa靶向脂质微泡能明显增加顺铂在卵巢癌A2780/DDP细胞中的浓度,且胞内药物浓度上调速率随时间逐渐减慢。Objective：To investigate the effects of the ultrasound combine with LHRHa-bound liposome microbubles（LHRHa-LM） in intracellur Cisplatin（DDP）concentration. Method：The human ovarian cancer cell line A2780/DDP was divided into 5 groups： control group,DDP group,DDP and ultrasound radiation group,DDP and LM plus ultrasound radiation group,and DDP and LHRHa-LM plus ultrasound radiation group.High Performance Liquid Chromatography（HPLC） was used to detect intracellular drug concentration at 12h,24h,48h after treatment for every group.Flow Cytometry（FCM） test was used to detect the cytomembrane permeability to propidine iodide（PI） instantly,12h,24h after liposome microbubles（LM）combined ultrasound irradiation in vitro A2780/DDP cell.Result： cytomembrane permeability to PI has increased instantly after treatment,and decreaced over time.DDP concentration is in linear dependence,R is 0.9994.DDP and LHRHa-LM plus ultrasound group demonstrated the most obvious increasing of intracellular drug concentration on 12h,24h after treatment.Conclusion： LHRHa-LM plus ultrasound could increase permeability of cell membrane more markedly than other groups,so to increase the intracellular chemotherapy drug concentration,and the rate of drug increasing may slower over time,that may be related to reversible increasing of cytomembrane permeability caused by LM plus ultrasound.

关 键 词：超声 靶向微泡 卵巢癌 顺铂 

分 类 号：R737.31[医药卫生—肿瘤]