顺铂纳米脂质体对骨肉瘤Saos-2细胞的杀伤作用及在荷瘤小鼠中的组织分布  

Lethal effects of nanoliposome encapsulated cisplatin on Saos-2 cells and its distribution in nude mice bearing human osteosarcoma xenografts

作　　者：王国文[1] 郭卫[1] 汤小东[1] 彭长亮[1] 赵会[1] 

机构地区：[1]北京大学人民医院骨与软组织肿瘤治疗中心,北京100044

出　　处：《北京大学学报（医学版）》2009年第5期525-530,共6页Journal of Peking University:Health Sciences

基　　金：首都医学发展科研基金(2005-1009)资助~~

摘　　要：目的:探讨顺铂纳米脂质体(NLE-CDDP)对人骨肉瘤细胞系Saos-2的杀伤作用及在荷瘤小鼠组织中的分布情况,并与单纯应用顺铂(CDDP)进行比较。方法:用含不同NLE-CDDP浓度的培养基培养人骨肉瘤细胞系Saos-2细胞,通过MTT、显微镜观察细胞形态,应用流式细胞分析技术检测该药对细胞生长的影响,以体内抑瘤实验检测NLE-CDDP对动物移植瘤生长的影响,用原子分光光度法测定荷瘤小鼠组织样品中的铂浓度。结果:经不同浓度的NLE-CDDP作用24～96 h,细胞存活率显著下降(P<0.05),在相同时间点NLE-CDDP抑制Saos-2细胞生长的作用优于CDDP。显微镜下观察显示部分细胞皱缩变形、崩解坏死,细胞脱壁悬浮;流式细胞术检查显示,细胞凋亡率逐渐增加,细胞周期各时相中S期的比例减少。NLE-CDDP对小鼠Saos-2肿瘤有明显的抗肿瘤活性。在注射1 h内,NLE-CDDP组血浆铂浓度是CDDP组的4.4倍;2 h后,CDDP组血液中已经无法检测出铂;24 h后,NLE-CDDP组血浆铂浓度还可以达到2.76μmol/L。在注射1 h内,NLE-CDDP组肾组织中铂浓度比CDDP组少50%;肝、脾、肿瘤中铂的浓度显著高于CDDP组(P<0.05);24 h后NLE-CDDP组脾组织中的铂浓度达最高峰。结论:顺铂纳米脂质体对Saos-2肿瘤的毒性高于单纯顺铂,其作用机制是延缓药物在体内循环中被快速清除。Objective：To investigate the killing effect of nanoliposome encapsulated cisplatin （NLE- CDDP） on human osteosarcoma cell line Saos-2 and explore the distribution of platinum （Pt） in tumorbearing mice. Methods： Saos-2 cells were cultured at different concentrations of NLE-CDDP. MTT assay,inverted microscopic observation and flow cytometry assay（FCM）were used to observe the antiproliferative effect of NLE-CDDP on the human osteosarcoma cells. Antitumor effect of NLE-CDDP was determined using the xenografts models of human osteosareoma cell Saos-2 in nude mice. The Pt concentration in the tissues of tumor-transplanted mice was determined by atomic spectrophotometer. Results： When treated at different concentrations of NLE-CDDP for 24 -96 hours, the survival rate of Saos-2 cells decreased significantly（P 〈0.05） ,At the same time point, the inhibitory effect of NLE-CDDP was stronger than that of CDDP; Degeneration and necrosis of Saos-2 cells increased; the apoptosis increased and the S phase reduced. This study demonstrated that NLE-CDDP had obvious anti-tumor activity. Within 1 hour of injection, in NLE-CDDP group plasma platinum concentration was 4.4-fold that in CDDP group; 2 hours later, platinum was not detected in the blood of CDDP group; 24 hours later, platinum still could be detected in NLE-CDDP group at 2.76μmol/L. During the first hour after injection of NLE-CDDP, the platinum content of the kidney was 50% less than that of CDDP group. Platinum in NLE-CDDP group showed rapid higher accumulation in the liver, spleen and tumor compared with CDDP group, and within 24 hours platinum reached the peak concentration in the spleen. Conclusion： The antitumor efficacy of NLE-CDDP on Saos-2 tumor is higher than that CDDP alone, and its mechanism is delaying rapid clearance from circulation.

关 键 词：骨肉瘤 顺铂 脂质体 纳米技术 

分 类 号：R738.1[医药卫生—肿瘤]