摘要
背景与目的:阿霉素是一种应用广泛的抗癌药物,肿瘤组织中阿霉素的浓度比血液浓度能更准确地反映其疗效。本研究采用肿瘤组织中阿霉素浓度的高效液相色谱检测法比较耐药KBv200细胞和敏感KB细胞裸鼠移植瘤组织中阿霉素的浓度。方法:建立KB、KBv200细胞裸鼠移植瘤模型,以高效液相色谱法检测肿瘤组织中阿霉素的浓度。色谱柱为反相BDSC18柱(250mm×4.6mm,ID5μm),流动相:乙腈/0.02mol/L磷酸二氢钾(1∶2.4,V/V,pH3.9);激发波长480nm,发射波长580nm;流速:1.0mL/min。结果:在所建立的色谱条件下,肿瘤组织中阿霉素的线性范围为29.3～7500ng/g,线性相关系数r=0.9998,最低检测浓度为14ng/g。在3750、468.8和117.2ng/g三个浓度的萃取回收率分别为(99.35±7.65)%、(99.79±5.73)%和(103.67±6.76)%,方法回收率分别为(91.89±7.03)%、(94.94±5.18)%、(100.83±5.32)%,日内及日间RSD均小于4.2%。在阿霉素注射后第1、3、5h,KBv200细胞裸鼠移植瘤组织中阿霉素的浓度分别为(139.32±54.68)、(260.00±126.11)和(173.26±13.88)ng/g,KB细胞裸鼠移植瘤组织中分别为(385.13±42.55)、(523.38±138.84)和(460.75±86.85)ng/g,在相同的时间点,KBv200细胞裸鼠移植瘤组织中阿霉素的浓度明显低于其敏感KB细胞株(P<0.05)。结论:采用高效液相色谱法测得耐药细胞肿瘤组织中抗癌药物的浓度低于相应的敏感细胞肿瘤组织。
BACKGROUND ＆ OBJECTIVE. Doxorubicin （Dox） is one of the most commonly used chemotherapeutic drugs. Drug concentrations in tumor tissue can predict the drug＇ s efficacy better than that in serum do. This study was to detect and compare the concentration of Dox in KBv200 and KB cell xenografts in nude mice by high-performance liquid chromatography （HPLC）. METHODS. Tumor models in nude mice were established with KB cells （drug-sensitive） and KBv200 cells （multidrug-resistant）. Dox was injected via the tail vein. The concentration of Dox in tumor tissue was detected by HPLC at 1, 3 and 5 h after injection. A Hypersil reversed-phase BDS C18 column （250 mm ×4.6 mm, ID 5 μm） and mobile phases that were composed of acetonitrile and 0.02 mol/L KH2PO4 （1/2.4, V/V, pH 3.9） at a flow rate of 1.0 mL/min were used for setting a fluorescence detector （excitation wave length was 480 nm; emission wave length was 580 nm）. RESULTS： Under the condition of HPLC, the calibration curve of Dox concentration in tumor tissue was linear within a range of 29.3-7 500 ng/g （r=0.9998）. The limit of detection in tumor tissue was 14 ng/g. At the concentration of 3 750, 468.8 and 117.2 ng/g, extraction recovery were （99.35±7.65）%, （99.79±5.73）% and （103.67±6.76）%, respectively, method recovery were （91.89±7.03）%, （94.94±5.18）% and （100.83±5.32）%, respectively. The relative standard deviation （RSD） of the intra-day and interday precision were less than 4.2%, At 1, 3, 5 h after Dox injection, the concentrations of Dox were （139.32±54.68）, （260.00±126.11） and （173.26± 13.88） ng/g in KBv cell xenografts, respectively, and （385.13±42.55）, （523.38 ±138.84） and （460.75 ±86.85） ng/g in KB cell xenografts, respectively. The Dox concentration was significantly higher in KB cell xenografts than in KBv200 cell xenografts at the same time point （P〈0.05）. CONCLUSION： Detected by HPLC, the concentration of Dox is much lower in multidrug-resistant cell
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2008年第4期364-368,共5页
Chinese Journal of Cancer
基金
国家自然科学基金资助项目(No30371659)~~
关键词
阿霉素
反相高效液相色谱
多药耐药
裸鼠移植瘤
肿瘤组织
药物浓度
Doxorubicin
High-performance liquid chromatography
Multidrug resistance
Nude mice
Xenograft
Tumor tissue
Drug concentration
