替莫唑胺缓释微球治疗胶质瘤皮下移植瘤的实验研究

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1、910SUZHOUUVIVERSITYJOURNALOFMEDICALSCIENCE2010;30(5)替莫唑胺缓释微球治疗胶质瘤皮下移植瘤的实验研究1212221吴自成，董军，项朝辉，周光华，黄强，兰青，吴新勇(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)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-7344胶质瘤细胞(1×10)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

2、代(2mm/3鼠)。待肿瘤生长至约65mm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-

3、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。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;裸小鼠中图分类号:R730．26405文献标识码:A文章编号:1673－0399(2010)05－0910－05PreliminarayStudiesonAnti-gliomaEffectofTemozolomid

4、eDelayed-ReleaseMicrospheresinSubcutaneousXenograftModel1212221WUZi-cheng，DONGJun，XIANGZhao-hui，ZHOUGuang-hua，HUANGQiang，LANQing，WUXin-yong(1．DeptofNeurosurgy，XinyiCityPeoplesHospital，JiangsuXinyi221400，China;2．DeptofNeurosurgy，the2ndHospitalAffiliatedtoSoochowUniv

5、ersity，JiangsuSuzhou215004，China)Abstract:ObjectiveToobservetheanti-gliomaeffectoftemozolomidedelayedreleasemicro-7spheresP-TMZinSHG-44subcutaneousxenograftmodel．MethodsTheSHG-44gliomacells(1×10)wereinoculatedsubcutaneouslyintotherightaxilofBalb/cnudemice．Thetumorwa

6、sresectedandcut3intopieces，andinoculatedsubcutaneously(2mm/mouse)．Whenxenografttumorsizereachedabout365mm，tumor-bearingmiceweredividedrandomlyintothe6groups(10mice/group)，namelyP-TMZgroup，TMZgroup，P-TMZplusTMZgroup，BCNUgroup，thenon-loadedmicrospheres(P-0)groupandnor

7、malsaline(NS)group．P-TMZ(500mg/kg)，andP-0(500mg/kg)weresuspendedwithDMEMtothefinalvolumeof150μlandinjectedslowlyintothetumors．TMZ(50mg/kg)wasadministeredwithgavageeverydayfor5days．BCNU(40mg/kg)wasinjectedintothetailveinonce，NSwasinjecteddi-rectly(150μl/mouse)intotum

8、ortissues．Tumorsizewasmeasuredevery4daystill28daysaftertreat-ment．ResultsTumorinhibitionratiosofP-TMZ，P-TMZplusTMZ，andBCNUweresignificantl