非致死剂量高强度聚焦超声逆转K562/AO2细胞多药耐药的实验研究  

The reversal effect of multidrug resistance by nonlethal dose-high intensity focused ultrasound in K562/AO2 cell line

作　　者：叶欣[1] 徐兴鲁[1] 沈绍华[1] 杨雪[1] 于连玲[1] 王军[1] 赵梅[1] 葛忠民[1] 杨宪勇[1] 亓春花[1] 

机构地区：[1]山东泰安市中心医院泰山医学院附属泰安医院肿瘤中心,271000

出　　处：《中华医学超声杂志（电子版）》2008年第4期16-21,共6页Chinese Journal of Medical Ultrasound(Electronic Edition)

摘　　要：目的探讨非致死剂量高强度聚焦超声(HIFU)逆转K562/AO2细胞多药耐药(MDR)的效能及其作用机制。方法(1)固定辐照时间或超声声强,应用不同声强或辐照时间的HIFU辐照K562、K562/AO2细胞株,观察HIFU的剂量-效应关系;(2)将K562/AO2细胞株分组为:阿霉素组(ADM组)、ADM加HIFU辐照组(HIFU组)、ADM加维拉帕米组(VRP组),分别观察各组细胞内的ADM浓度、细胞的抑制率和细胞凋亡情况;(3)检测HIFU干预前后K562/AO2细胞的P-gp、PDCD5表达情况。结果(1)当辐照时间一定时(5 s)声强越高肿瘤细胞存活率越低,当HIFU声强一定时(400 W/cm2)细胞存活率随HIFU辐照时间延长而下降;(2)在K562/AO2细胞株中HIFU、VRP干预均能提高细胞内ADM浓度,HIFU组、VRP组与ADM组比较P均<0.01,HIFU组与VRP组比较P>0.05;HIFU组、VRP组、ADM组均能抑制K562/AO2细胞的增殖和促使K562/AO2细胞发生凋亡,HIFU组、VRP组与ADM组比较P均<0.01,HIFU组与VRP组比较P>0.05;(3)HIFU辐照K562/AO2细胞后P-gp表达明显降低,PDCD5表达升高。结论非致死剂量HIFU辐照K562/AO2细胞能够提高耐药肿瘤细胞内的化疗药物浓度,增加耐药肿瘤细胞的抑制率和凋亡率。非致死剂量HIFU逆转MDR的可能机理是下调耐药细胞的P-gp表达和上调PDCD5表达。Objective To study and evaluate the reversal effect of multi-drug resistance （MDR） and the mechanism by non-lethal dose-high intensity focused ultrasound （HIFU）in the K562/AO2 cell lines. Methods （ 1 ） With fixed exposure or acoustic intensity, the relationship between tumor cell livability and HIFU dosage was observed by different acoustic intensity and HIFU exposure duration in the K562, K562/AO2 cell lines; （2） The K562 and K562/AO2 cell lines were classified into groups： adriamycin （ADM） ; adriamycin plus HIFU and adriamycin plus verapamil （VRP）. The intracellular adriamycin concentration, cell proliferation and apoptosis ratio were assessed; （3）The P-gp and PDCD5 expression of K563/AO2 cells were examined before and after application of HIFU. Results （ 1 ） With the fixed exposure duration （5 s）, the tumor cell livability decreased along with an increase of the ultrasound intensity; With the fixed acoustic intensity （400 W/cm^2）, the cell survival reduced along with a longer exposure duration by HIFU; （2） The intracellular adriamycin concentration increased by both HIFU and VRP （P 〈 0.01 ） compared to ADM group. No significance was observed between HIFU and VRP groups; The inhibition of cell proliferation and apoptosis for K562/AO2 were found in all groups （P 〈 0.01 ）, but no statistical difference between group HIFU and VRP （P 〉 0.05）. （3） The P-gp expression of K562/AO2 decreased and PDCD5 increased after HIFU and PDCD5 increased. Conclusions Non-lethal dose-HIFU can effectively increase intraeellular eytotoxic adriamycin concentration and increased cellular proliferation inhibition and apoptosis ratio in K562/AO2 as results. The mechanism of its reversal effect may be upregulation of PDCD5 and downregulation of P-gp.

关 键 词：超声疗法 K562细胞 药物耐受性 高强度聚焦超声 

分 类 号：R363[医药卫生—病理学]