替莫唑胺缓释微球治疗胶质瘤皮下移植瘤的实验研究  

Preliminaray Studies on Anti-glioma Effect of Temozolomide Delayed-Release Microspheres in Subcutaneous Xenograft Model

作　　者：吴自成 董军[2] 项朝辉 周光华[2] 黄强[2] 兰青[2] 吴新勇 

机构地区：[1]江苏省新沂市人民医院神经外科,江苏新沂221400 [2]苏州大学附属第二医院神经外科,江苏苏州215004

出　　处：《苏州大学学报（医学版）》2010年第5期910-914,共5页Suzhou University Journal of Medical Science

基　　金：国家自然科学基金资助项目(30400457)

摘　　要：目的观察替莫唑胺缓释微球(P-TMZ)对SHG-44人脑胶质瘤皮下移植瘤的抑瘤效应。方法将SHG-44胶质瘤细胞(1×107)注射于Balb/c裸小鼠右腋皮下,再将皮下移植瘤以组织块接种的方法皮下传代(2mm3/鼠)。待肿瘤生长至约65mm3时,将荷瘤鼠随机分为瘤内注射替莫唑胺缓释微球(P-TMZ)组、替莫唑胺(TMZ)组、P-TMZ+TMZ联合用药组、卡莫斯汀(BCNU)组、空白微球(P-0)组和生理盐水(NS)组,每组10只鼠。将P-TMZ(500mg/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肿瘤组织内;TMZ以50mg/kg灌胃,每日一次,连续5d;BCNU以40mg/kg尾静脉注射一次;NS以150μl瘤内注入。每4d测量荷瘤鼠肿瘤大小直至治疗后28d。结果 P-TMZ、P-TMZ+TMZ和BCNU组抑瘤率均明显高于P-0、NS组(P<0.01),且抑瘤效应优于TMZ组(P<0.05);TMZ组抑瘤率高于P-0、NS组(P<0.05)。结论 P-TMZ保留了TMZ的抑瘤活性,在局部应用时抑瘤效果优于TMZ。Objective To observe the anti-glioma effect of temozolomide delayed release microspheres P-TMZ in SHG-44 subcutaneous xenograft model. Methods The SHG-44 glioma cells（ 1 × 107） were inoculated subcutaneously into the right axil of Balb/c nude mice. The tumor was resected and cut into pieces,and inoculated subcutaneously （ 2 mm3 /mouse） . When xenograft tumor size reached about 65mm3,tumor-bearing mice were divided randomly into the 6 groups （ 10 mice/group） ,namely P-TMZ group,TMZ group,P-TMZ plus TMZ group ,BCNU group,the non-loaded microspheres （ P-0） group and normal saline （ NS） group. P-TMZ（ 500 mg/kg） ,and P-0（ 500 mg/kg） were suspended with DMEM to the final volume of 150μl and injected slowly into the tumors. TMZ（ 50 mg/kg） was administered with gavage everyday for 5 days. BCNU（ 40 mg/kg） was injected into the tail vein once,NS was injected directly （ 150 μl/mouse） into tumor tissues. Tumor size was measured every 4 days till 28 days after treatment. Results Tumor inhibition ratios of P-TMZ,P-TMZ plus TMZ ,and BCNU were significantly higer than P-0 and NS（ P 0. 01） ; P-TMZ,P-TMZ plus TMZ and BCNU were more effective than TMZ （ P 0. 05） . TMZ showed definite anti-tumor effect when compared with P-0,NS （ P 0. 05） . Conclusion P-TMZ retaines anti-tumor activity of TMZ and has better therapeutic effect against glioma when administered locally.

关 键 词：胶质瘤 SHG-44胶质瘤细胞 皮下移植瘤 替莫唑胺 缓释微球 裸小鼠 

分 类 号：R730.264.05[医药卫生—肿瘤]