透明质酸修饰载紫杉醇脂质体抑制脑肿瘤干细胞的初步评价舒小镭1.DOC

透明质酸修饰载紫杉醇脂质体抑制脑肿瘤干细胞的初步评价 舒小镭何笑冬李倩 1重庆医科大学基础医学院，重庆400016 2重庆市肿瘤医院放射治疗科 摘要 目的 制备透明质酸（HA）修饰载紫杉醇靶向脂质体（HALP-PTX），考察其对CD44阳性表达的脑胶质瘤肿瘤干细胞的亲和力和抑制效果。方法采用薄膜分散法制备HALP-PTX，细胞摄取试验考察透明质酸与肿瘤干细胞的亲和力。MTT实验考察脂质体对肿瘤干细胞的增殖抑制效果。用肿瘤干细胞构建原位移植瘤动物模型，考查不同脂质体对荷瘤裸鼠的生存期的影响。结果肿瘤干细胞对HALP的摄取能力显著大于LP，脑肿瘤干细胞对经透明质酸修饰的脂质体的摄取效率是普通脂质体的2.8倍，差异具有统计学意义（P0.01）；HALP-PTX对肿瘤干细胞的生长的抑制作用显著强于LP-PTX,HALP-PTX能够显著延长荷瘤裸鼠的中位生存期，生理盐水组、PTX组、LP-PTX组和HALP-PTX组的中位生存期分别为19天、23天、29天和41天。结论 与PTX以及LP-PTX相比，HALP-PTX能够更加有效的被脑肿瘤干细胞识别和摄取，抑制肿瘤细胞的增殖，具有更强的抗肿瘤作用。 关键词 透明质酸；紫杉醇；脂质体；肿瘤干细胞 Study on Hyaluronic Acid modified paclitaxel loaded liposome inhibit brain tumor stem cell Shu xiao-lei1，He xiao-dong1，Li qian1，Wang ying2，Li shao-lin1* 1Faculty of basic medical sciences, Chongqing medical university 2 tumor radiotherapy, Chongqing cancer?hospital Abstract Objective：To prepare Hyaluronic Acid conjugated paclitaxel loaded liposome and evaluate the efficiency of cellular uptake and the efficiency of inhibiting brain cancer stem cell．MethodsLiposome was prepared byfilm-ultrasonic method.Cellular uptake by brain tumor stem cell was explored.The anti-proliferation efficiency of HALP-PTX was evaluated by MTT assay. Brain tumor stem cells were used to build orthotopic tumor model, which were used to evaluate the effect of anti-cancer. ResultsThe evaluation of cells uptake showed HALP is a good delivery system for brain tumor stem cell. The anti-proliferative activity against brain tumor stem cell confirmed strong inhibitory effect of HALP-PTX. HALP-PTXcan significantlyprolongmedian survivalof nude.Conclusion Comparing with PTX and LP-PTX，HALP-PTX could more persistently inhibit the proliferation of brain tumor stem cell. Thus, HALP-PTX, as a new nanometer drug, has a special application value for the therapy of brain tumor stem cell. Key words: Hyaluronic Acid;paclitaxel; Liposome;tumor stem cell 脑胶质瘤是最常见的脑部肿瘤疾病，占全部颅内肿瘤的40%以上。手术治疗是脑胶质瘤临床治疗的首选方案。然而由于脑胶质瘤本身是浸润生长，不易与正常的脑组织区分，因此在手术过程中很难将肿瘤组织全部切除[1]。对较高级别脑胶质瘤的治疗至今尚无突破性进展，近20年来，胶质瘤患者的中位生存期无明显改善。