替莫唑胺缓释剂胶质瘤间质内化疗的实验研究  

Experimental study of interstitial chemotherapy against glioma with sustained-release temozolomide

作　　者：周光华[1] 董军[1] 吴自成[1] 马辉[1] 陈宝敏[1] 黄强[1] 兰青[1] 杨海龙[2] 王国成[2] 

机构地区：[1]苏州大学附属第二医院神经外科,江苏苏州215004 [2]天津天士力研究院化学制药研究所,天津300402

出　　处：《中国微侵袭神经外科杂志》2008年第10期455-458,共4页Chinese Journal of Minimally Invasive Neurosurgery

基　　金：国家自然科学基金资助项目(编号:30400457;30772241);江苏省科技厅青年科技创新人才项目资助(编号:BK2007507)

摘　　要：目的观察肿瘤间质内应用替莫唑胺缓释剂(P-TMZ)对人脑胶质瘤的抑瘤效应。方法先以MTT法测定P-TMZ对SHG-44胶质瘤细胞的抑瘤效应,加药96h后检测不同药物浓度在570nm处的OD值,计算其IC50;再将SHG-44细胞接种于NC系裸小鼠右腋皮下,待肿瘤生长至体积约100mm3时,将荷瘤鼠随机分为P-TMZ组、替莫唑胺(temozolomide,TMZ)组、卡莫斯汀(BCNU)组和不载药微球(P-0)组,然后将P-TMZ(500mg/kg)、TMZ(50mg/kg)、BCNU(40mg/kg)和P-0(500mg/kg)以DMEM培养液混悬至终体积150μl,经皮多点穿刺缓慢注入相应组肿瘤间质内,每周测量皮下肿瘤大小2次。结果P-TMZ、TMZ和BCNU对SHG-44胶质瘤细胞的体外抑瘤效果明显,三者的IC50均<10μg/ml;与P-0组比较,差异均具有统计学意义(P<0.01)。在体内抑瘤实验中,P-TMZ、BCNU、TMZ抑瘤率均明显高于P-0(P<0.01)。P-TMZ和BCNU的抑瘤效应优于TMZ组(P<0.05)。结论P-TMZ保留了TMZ的抑瘤活性,兼具高稳定性和长时程药物作用时间等药代动力学特征,为胶质瘤病人肿瘤残腔内间质化疗提供了新的治疗选择。Objective To observe the anti-tumor effect of interstitial chemotherapy with sustained-release temozolomide (P-TMZ) against glioma. Methods Anti-tumor effect of P-TMZ in vitro on human glioma cell line SHG-44 was evaluated by MTT assay. OD570 value of drugs with series dilution was detected after 96 h. IC50 of each drug was calculated based on inhibition ratios. The SHG-44 cells were inoculated subcutaneously into the right axil of NC nude mice. When the size of xenograft tumor reached 100 mm3, tumor-bearin...

关 键 词：神经胶质瘤 替莫唑胺 迟效制剂 药物疗法 

分 类 号：R739.4[医药卫生—肿瘤]