叶钢, 宋晓峰, 张荣贵, 刘为池. 经尿道灌注自杀基因治疗大鼠膀胱癌的实验研究[J]. 中国肿瘤临床, 2004, 31(18): 1054-1056.
引用本文: 叶钢, 宋晓峰, 张荣贵, 刘为池. 经尿道灌注自杀基因治疗大鼠膀胱癌的实验研究[J]. 中国肿瘤临床, 2004, 31(18): 1054-1056.
Ye Gang, Song Xiao-feng, Zhang Rong-gui, . Suicide Gene Therapy for Rat Bladder Carcinoma Entailing Instillation of Bladder via Urethra[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2004, 31(18): 1054-1056.
Citation: Ye Gang, Song Xiao-feng, Zhang Rong-gui, . Suicide Gene Therapy for Rat Bladder Carcinoma Entailing Instillation of Bladder via Urethra[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2004, 31(18): 1054-1056.

经尿道灌注自杀基因治疗大鼠膀胱癌的实验研究

Suicide Gene Therapy for Rat Bladder Carcinoma Entailing Instillation of Bladder via Urethra

  • 摘要: 目的:探讨经尿道膀胱灌注脂质体和逆转录病毒载体介导的自杀基因(HSVtk),观察在羟基无环鸟苷(ganciclovir,GCV)作用下大鼠膀胱肿瘤的生长情况。方法:用N-甲基-亚硝基脲(MNU)膀胱灌注建立大鼠原位膀胱癌模型。经尿道膀胱灌注脂质体、逆转录病毒载体HSVtk基因,随后腹腔内注射GCV,连续6天。结果:经尿道膀胱灌注HSVtk基因后48h,RT-PCR检测出膀胱肿瘤中HSVtk基因表达。逆转录病毒组和脂质体组膀胱总重量与裸质粒组和对照组相比有显著差异,表明膀胱肿瘤的生长被抑制。TUNEL法原位检测肿瘤组织中凋亡细胞不仅出现在表层细胞,而且深层细胞大量凋亡,推测旁观者效应可能发挥了一定作用。结论:经尿道膀胱灌注脂质体DNA或重组逆转录病毒载体可以向肿瘤转导HSVtk基因。HSVtk/GCV系统能抑制大鼠原位膀胱肿瘤的生长,显示出抗肿瘤作用。

     

    Abstract: Objective : The growth of orthotopic bladder tumor in rat entailing instillation of liposome/DNA complex and retroviral vectors containing HSVtk gene was evaluated with GCV treatment. Methods : Orthotopic bladder tumors were established in rats by intravesical administration of MNU (N-mmethyl-noitrosourea). The therapeutic protocol then entailed instillation of liposome/DNA complex or a retroviral vector containing the HSVtk suicide gene into rat bladder followed by a 6-day-term reg-imen of intraperitoneal GCV injections. Results : Forty-eight hours after intravesical instillation of HSVtk gene, RT-PCR analysis of rat bladder tumors demonstrated the expression of HSVtk. The bladder including tumor in retroviral vector group and liposome/DNA group weighted less than that in naked DNA group or in control group. This revealed that the tumor growth was significantly inhibited.TUNEL assays showed that the apoptosis cells existed from superficial cells into deeper tissue, which is account for role of bystander effect. conclusion : HSVtk gene could be transferred into bladder tumor entailing instillation of liposome/DNA complex and retroviral vectors through the urethra. HSVtk/GcV system inhibits the growth of an experimental rat orthotopic bladder cancer, showing anti-tumor effect.

     

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