甲氧基聚乙二醇-聚乳酸胶束载体对丝裂霉素的抑瘤活性及局部组织损伤的影响  

Effect of mitomycin modified with methoxy polyethylene glycol-polylactic acid on tumor inhibition and tissue injury of rats

作　　者：岳长来[1] 张浩[1] 李鸿[1] 孙岚[1] 张英鸽[1] 

机构地区：[1]军事医学科学院毒物药物研究所纳米药理毒理学重点实验室,北京100850

出　　处：《中国药理学与毒理学杂志》2010年第5期349-353,共5页Chinese Journal of Pharmacology and Toxicology

基　　金：国家重点基础研究发展计划资助(973计划)(2006CB933304);国家重点基础研究发展计划资助(973计划)(2010CB933904);国家高技术研究发展计划(863计划)资助项目(2006AA03Z333)~~

摘　　要：目的探讨甲氧基聚乙二醇-聚乳酸(mPEG-PLA)胶束是否可以提高丝裂霉素(MMC)的抗肿瘤活性及降低MMC的局部组织损伤作用。方法采用腹腔种植方法分别制备昆明小鼠肉瘤180(S180)实体瘤模型及H22肝癌腹水瘤模型,每个模型小鼠均分为模型组(生理盐水0.1ml·kg-1),mPEG-PLA组,MCC1mg·kg-1组,胶束MMC2,6和18mg·kg-1组。分别观察S180实体瘤的抑瘤率及H22腹水瘤的生命延长率。BALB/C小鼠分别右后肢im给予生理盐水组(正常对照),mPEG-PLA,胶束MMC0.02,0.04,0.08,0.1,0.16,0.2和0.4mg·kg-1组,MMC0.02,0.04,0.08,0.1,0.16,0.2和0.4mg·kg-1组,观察小鼠局部组织损伤情况。结果在S180实体瘤模型上,mPEG-PLA无肿瘤抑制作用;MMC1mg·kg-1的肿瘤抑制率为34.8%,胶束MMC2,6和18mg·kg-1的肿瘤抑制率分别为31.23%,51.8%,66.8%,胶束MMC6和18mg·kg-1的肿瘤抑制率明显高于MMC组(P<0.01)。在H22腹水癌模型上,mPEG-PLA对肿瘤小鼠的生命延长率无影响;MMC1mg·kg-1的生命延长率为123.4%,胶束MMC2,6和18mg·kg-1的生命延长率分别为76.6%,171.0%和206.5%,胶束MMC2mg·kg-1组生命延长率显著低于MMC组(P<0.01),但高于模型组(P<0.01),胶束MMC6和18mg·kg-1的生命延长率明显好于MMC组(P<0.05)。在组织损伤模型上,胶束MMC组损伤发生时间和损伤面积明显低于相同剂量的MMC组(P<0.05)。结论 mPEG-PLA胶束能够提高MMC体内抗肿瘤作用,降低MMC的毒性作用。OBJECTIVE To explore whether methoxy polyethylene glycol-polylactic acid ( mPEG-PLA) could affect the anti-cancer effect of mitomycin ( MMC) in vivo and reduce the tissue injury. METHODS This experiment had two parts: a sarcoma 180 ( S180) mice model to observe the tumor weight and tumor inhibition rate as well as an H22 ascitic tumor model to observe survival time and life elongation rate. Mice were divided into the model group,MMC 1 mg·kg-1 group, mPEG-PLA-MMC 2,6 and 18 mg·kg-1 group and mPEG-PLA group. BALB/C mice were used in the tissue injury experment. The mice were divided into the normal control group,MMC 0. 02, 0. 04,0. 08,0. 10,0. 16,0. 20 and 0. 40 mg·kg-1 group,mPEG-PLA-MMC 0. 02,0. 04,0. 08, 0. 10,0. 16,0. 20,and 0. 40 mg·kg-1 groups and mPEG-PLA group. RESULTS mPEG-PLA had no anti-cancer effect on tumor weight,tumor inhibition rate and survival time in the two model groups. The tumor inhibition rate of mPEG-PLA-MMC 2,6 and 18 mg·kg-1 was 31. 23% ,51. 78% and 66. 80% ,respectively while in MMC 1 mg·kg-1 group it was 34. 78% . The tumor inhibition rate of mPEG-PLA-MMC 6 and 18 mg·kg-1 was significantly increased compared with MMC 1 mg· kg-1( P < 0. 01) . Ascetic tumor H22 results indicated that mPEG-PLA-MMC could lengthen the life of tumor-bearing mice in vivo. The life-elongation rates of mPEG-PLA-MMC 2,6 and 18 mg·kg-1 were 76. 6% ,171. 0% and 206. 5% ,respectively while the life-elongation rate in MMC 1 mg·kg-1 group was 123. 4% . Compared with MMC,the life-elongation rate in mPEG-PLA-MMC 2 mg·kg-1 was shortened( P < 0. 01) ,but higher than in model group( P < 0. 01) . The life-elongation rates of mPEG-PLA-MMC 6 and 18 mg·kg-1 were significantly increased ( P < 0. 05) . Tissue injury showed that there was significant difference between mPEG-PLA-MMC groups and MMC groups ( P < 0. 05, P < 0. 01) . CONCLUSION mPEG-PLA could remarkably reinforce the anti-cancer effect of MMC in vivo and significantly reduce the tissue injury.

关 键 词：丝裂霉素 肉瘤S180 H22腹水瘤 化学修饰 药物毒性 聚乙二醇-聚乳酸 

分 类 号：R96[医药卫生—药理学]