基因重组腺相关病毒介导内皮抑素治疗祼鼠膀胱癌

目的 观察重组腺相关病毒(rAAV)-内皮抑素(Endostatin,ES)(简称rAAV-ES)基因治疗膀胱癌的效果.方法 T24细胞悬液接种于BALB/C裸鼠右侧肩胛区皮下,取已成瘤裸鼠随机分为3组:对照组、rAAV-多克隆位点(MCS)组、rAAV-ES组,每组5只,分别瘤内注射生理盐水、rAAV-MCS及rAAV-ES,4周后处死荷瘤裸鼠,取出移植瘤,常规苏木素-伊红(HE)染色、计算微血管密度(MVD);采集裸鼠血液标本酶联免疫吸附试验(ELISA)检测血清中ES浓度.结果 (1)瘤内注射rAAV-ES 9 d后,肿瘤生长明显抑制,治疗4周后:各组肿瘤体积分别是:rAAV-ES组(0.75±0.08)cm~3、rAAV-MCS组(1.27±0.13)cm~3和对照组(1.24±0.17)cm~3;组间比较差异有统计学意义(P＜0.05);(2)各组移植瘤MVD分别:rAAV-ES组(18.72±2.53)个/HP、rAAV-MCS组(52.38±6.46)个/HP和对照组(49.94±7.17)HP;rAAV-ES组显著低于对照组和rAAV-MCS组(P＜0.05).结论 rAAV-ES能抑制膀胱癌的血管生成和肿瘤的生长.

Effects of gene therapy by rAAV-Endostatin in treatment of bladder cancer:an experimental study in vivo

Objective To construct bladder cancer animal model using unde mice and study thetherapeutic effect of recombinant adeno-associated vires(rAAV)-endostatin(ES)in vivo.Methods Cell suspension of T24 cells were subcutaneously injected into the fight scapular region of nude mice.The nude mice bearing tumors were randomly divided into 3 groups:rAAV-multiple cloning site(MCS)group,rAAV-ES group and control group.After treatment for 4 weeks.the nude mice were killed and the tumor volume was compared.At the Same time.blood ES concentration wag assayed by enzyme-linked immuosorbent assay(ELISA).Results At the 4th week after injection of rAAV-ES,the tumor volume in rAAV-ES group,rAAV-MCS group and control group was(0.75±0.08)cm~3,(1.27±0.13)cm~3 and(1.24±0.17)cm~3.The microvessel density(MVD)WaS(18.72±2.53)/HP,(52.38±6.46)/HP and (49.94±7.17)/HP,respectively.Conclusion rAAV-ES was successfidly constructed,and it could in hibit angiogenesis.