腔内灌注重组分泌型内皮抑素腺相关病毒治疗膀胱癌的实验研究

Intravesical perfusion of recombinant adeno-associated virus-endostatin in treatment of bladder cancer： experiments with mice

目的研究膀胱腔内灌注重组分泌型内皮抑素腺相关病毒（rAAV—ES）治疗膀胱癌的疗效。方法建立C57BL／6小鼠原位膀胱癌模型；膀胱腔内灌注rAAV—ES后检测肿瘤生长情况，分析抑瘤率和小鼠生存期，并与对照组进行比较。结果成功建立小鼠原位膀胱癌模型；膀胱腔内灌注rAAV—ES后荷瘤膀胱重量（145mg±30mg）较rAAV—EYFP组（250mg±32mg）和PBS组（250mg±30mg）轻（均P〈0．05），计算抑瘤率均为42％；实验组小鼠生存期（46d±7d）长于对照组（38d±7d和38d±6d）（均P〈0．05）。结论膀胱腔内灌注rAAV—ES可成功抑制肿瘤的血管生成，从而抑制膀胱癌的发生、发展，rAAV—ES是膀胱癌基因治疗的有效生物制剂。

Objective To study the anti-tumor effect of intravesical perfusion of recombinant adeno- associated virus-endostatin （rAAV-ES） in treatment of bladder cancer. Methods Forty-five C57BL/6 mice underwent intravesical perfusion of mouse bladder cancer cells of the line MB49 so as to establish orthotopic murine bladder cancer models and were divided into 3 equal groups, 3 days later to undergo intravesical perfusion of rAAV-ES, rAAV-EYFP,and PBS respectively once per week for 6 times. The anti-tumor effect of rAAV-ES on the tumor bearing mice was studied. Results The tumor weight of the rAAV-ES group was （ 145 ± 30） mg, significantly lighter than those of the rAAV-EYFP and PBS groups [ （250 ± 32） mg and （250 ± 30） mg respectively, both P 〈0. 05]. The survival time of the rAAV-ES-treated mice was （46 ± 7） d, significantly longer than those of the rAAV-EYFP- and PBS-treated groups [ （ 38 ± 7 ） d and （ 38 ± 6） d respectively, both P 〈 0. 05 ]. Conclusion An effective biologic agent in bladder cancer gene therapy, intravesical treatment with rAAV-ES inhibits the angiogenesis, thus inhibiting the tumor formation and progression.