The efficacy of abraxane on osteosarcoma xenografts in nude mice and expression of secreted protein, acidic and rich in cysteine

摘要

Background: Although there have been previous efforts to optimize dose intensity or change the chemotherapy protocol for osteosarcoma, long-term survival has not been markedly improved during the past 15 years. METHOD:: Nude mice bearing established OS-732 human osteosarcoma received varying doses of Adriamycin, paclitaxel and Abraxane to assess tumor growth inhibition. For the dose-response experiments, mice were treated with the following agents at the indicated doses: (A) Adriamycin (2.5 mg/kg, ip), (B) paclitaxel (20 mg/kg, ip), (C-E) Abraxane (10, 20 and 40 mg/kg, ip, respectively) and (F) Saline (20 mg/kg, ip). All agents were administered every 4 days. Mean tumor volume and mice weight measurements were recorded every 3 days. Tumor weights were examined after mice were killed. Real-time polymerase chain reaction and Western blot were used to detect the expression levels of secreted protein, acidic and rich in cysteine (SPARC) in osteosarcoma specimens. Results: Administration of 40 mg/kg Abraxane showed a tumor inhibitory rate of 98.8% (tumor weight, 0.033 ± 0.044 g, P < 0.01), which was significantly higher than Adriamycin (46.1%, tumor weight, 1.455 ± 1.115 g, P < 0.01) and paclitaxel (40.8%, tumor weight, 1.597 ± 1.834 g, P < 0.05). Real-time polymerase chain reaction and Western blot showed higher expression of SPARC in tumor tissues than in normal tissues. Conclusion: The antitumor effect of Abraxane was demonstrated in osteosarcoma xenografts in vivo. It suggests that SPARC tends to be highly expressed in osteosarcoma and further experiments need to explore its clinical relevance and the possible mechanisms.