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目的观察重组分泌型内皮抑素腺相关病毒(rAAV-ES)在裸鼠模型体内的抗肿瘤作用。方法以rAAV-ES转染(转染复数MOI=1×10~5)膀胱癌细胞(EJ)后建立裸鼠肿瘤模型,检测EJ细胞被转染后的成瘤率及肿瘤生长情况;裸鼠肌注rAAV-ES后检测内皮抑素在体内的表达;建立裸鼠肿瘤模型,检测全身应用rAAV-ES后抑制肿瘤发展的作用、对肿瘤微血管密度(MVD)的影响及其毒副作用。结果被rAAV-ES转染的EJ细胞成瘤率仅为对照组的2/5;体内实验证实肌注rAAV-ES后血清中内皮抑素长期高效表达(30～40)μg/L;全身应用后肿瘤生长速度减慢(32±9)d,瘤体微血管密度变低(8.30±3.14)/0.739 mm~2,心脑组织学检查未见缺血和其他异常改变。结论rAAV-ES无毒副作用,可有效地抑制肿瘤的血管生成,从而抑制膀胱癌的发生、发展,其成功包装为原位基因治疗膀胱癌奠定了基础。
Objective To observe the antitumor effect of recombinant human endostatin-associated adenovirus (rAAV-ES) in nude mice. Methods The tumor model of nude mice was established by transfection with rAAV-ES (MOI = 1 × 10 ~ 5) bladder cancer cells (EJ), and the tumorigenic rate and tumor growth of EJ cells were detected. The expression of endostatin in vivo was detected by intramuscular injection of rAAV-ES. A nude mouse model of tumor was established to detect the effect of systemic administration of rAAV-ES on tumor development and its effect on tumor microvessel density (MVD) and its toxic and side effects. Results The tumorigenic rate of EJ cells transfected with rAAV-ES was only 2/5 of the control group. The in vivo experiments demonstrated that endostatin was highly expressed in serum (30-40 μg / L) after rAAV-ES administration in vivo. The tumor growth rate slowed down (32 ± 9) d, tumor microvessel density (8.30 ± 3.14) /0.739 mm2, no ischemic and other abnormal changes in brain and brain tissue. Conclusions rAAV-ES has no toxic and side effects and can effectively inhibit the angiogenesis of tumor, thus inhibiting the occurrence and development of bladder cancer. The successful packaging of rAAV-ES laid the foundation for the in situ gene therapy of bladder cancer.