Wang Guo Wen, Guo Wei, Tang Xiao Dong, Peng Chang Liang, Zhao Hui
Department of Orthopaedic Oncology, Peking University People's Hospital, Beijing 100044, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2009 Oct 18;41(5):525-30.
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 tumor-bearing mice.
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 osteosarcoma cell Saos-2 in nude mice. The Pt concentration in the tissues of tumor-transplanted mice was determined by atomic spectrophotometer.
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 2.76 mumol/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.
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.
研究纳米脂质体包裹顺铂（NLE-CDDP）对人骨肉瘤细胞系Saos-2的杀伤作用，并探讨铂（Pt）在荷瘤小鼠体内的分布。
用不同浓度的NLE-CDDP培养Saos-2细胞。采用MTT法、倒置显微镜观察和流式细胞术（FCM）观察NLE-CDDP对人骨肉瘤细胞的抗增殖作用。利用人骨肉瘤细胞Saos-2裸鼠异种移植模型测定NLE-CDDP的抗肿瘤作用。用原子分光光度计测定荷瘤小鼠组织中的Pt浓度。
用不同浓度的NLE-CDDP处理24-96小时后，Saos-2细胞存活率显著降低（P<0.05）。在同一时间点，NLE-CDDP的抑制作用强于顺铂（CDDP）；Saos-2细胞的变性和坏死增加；细胞凋亡增加，S期减少。本研究表明NLE-CDDP具有明显的抗肿瘤活性。注射后1小时内，NLE-CDDP组血浆铂浓度是CDDP组的4.4倍；2小时后，CDDP组血液中未检测到铂；24小时后，NLE-CDDP组仍能检测到铂，浓度为2.76μmol/L。注射NLE-CDDP后的第1小时内，肾脏中的铂含量比CDDP组少50%。与CDDP组相比，NLE-CDDP组的铂在肝脏、脾脏和肿瘤中的积累迅速且更高，并且在24小时内铂在脾脏中达到峰值浓度。
NLE-CDDP对Saos-2肿瘤的抗肿瘤疗效高于单独使用CDDP，其机制是延迟从循环中的快速清除。
