[Lethal effects of nanoliposome encapsulated cisplatin on Saos-2 cells and its distribution in nude mice bearing human].
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 tumor-bearing 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 osteosarcoma 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 2.76 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.


CONCLUSIONS
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.
Wang
Guo Wen
GW
Department of Orthopaedic Oncology, Peking University People's Hospital, Beijing 100044, China.
Guo
Wei
W
Tang
Xiao Dong
XD
Peng
Chang Liang
CL
Zhao
Hui
H
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004337:Drug Carriers; D005260:Female; D006801:Humans; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D002945:Cisplatin