聚谷氨酸天冬氨酸顺铂复合物的体内毒性和抑瘤活性  

Study on the in vivo toxicity and antitumor activity of poly(γ-glutamic acid)asp-cisplatin complex

作　　者：耿旭[1,2] 黄静[1] 劳勋[1] 吴自荣[1] 

机构地区：[1]华东师范大学生命科学学院,上海200062 [2]河南大学医学院,河南开封475004

出　　处：《中国医院药学杂志》2012年第13期1005-1009,共5页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金资助项目(编号:31170920);国家科技部863资助项目(编号:2009AA03Z429)

摘　　要：目的:研究聚谷氨酸天冬氨酸顺铂复合物(PGA-Asp-CDDP)的体内毒性和抑瘤活性。方法:采用透析法、MMT法、昆明鼠和BALB/c裸鼠SMMC-7721肝癌模型检测PGA-Asp-CDDP的缓释作用,细胞毒性,体内毒性和抑瘤活性。结果:PGA-Asp-CDDP的10 h时顺铂累计释放率为32%,与人肝癌细胞SMMC-7721孵育72 h的IC50为(45.5±10.3),累计给药为12 mg·kg-1时体内毒性显著下降,并且对肝癌模型有显著抑瘤效果(P<0.01)。结论:聚谷氨酸天冬氨顺铂复合物有望成为治疗肝癌的一种安全有效的药物。OBJECTIVE To evaluate in vivo toxicity and antitumor activity of poly （γ-glutamic acid）asp-cisplatin complex （PGA-Asp-CDDP）. METHODS The release profile of PGA-Asp-CDDP was studied with a dialysis method. The cytotoxicity of the complex was detected by MTT assay. In vivo toxicity of the complex was performed in KM mice and its anti-tumor effect was evaluated in human hepatoma cell SMMC 7721 grafted mice. RESULTS CDDP could be gradually released from PGA Asp-Pt in physiological saline at 37 ℃ and the accumulative released rate was 32% at 10 h. The IC50 value of PGA-Asp- CDDP was 45. 5±10. 3 against SMMC-7721 cell when incubation at 72 h. In vivo experiments showed that the toxicity of PGA-Asp-CDDP significantly decreased at the cumulative administration concentration of 12 mg·kg^-1 and PGA-Asp-CDDP treatment had significantly higher antitumor activity than control treatment （P〈0. 01）. CONCLUSION PGA-Asp-CDDP may become a safe and effective drug for the treatment of liver cancer.

关 键 词：聚谷氨酸 顺铂 毒性 抑瘤活性 

分 类 号：R963[医药卫生—微生物与生化药学]