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.