目的:研究肿瘤特异性双自杀基因载体系统pc-ChCDTK对视网膜母细胞瘤的体内杀伤作用。方法:用G418筛选载体阳性转染的Y79细胞;通过皮下注射载体转染和未转染的Y79细胞致瘤BALB/C小鼠,每组10只。Y79细胞皮下移植术7d后,向成瘤裸小鼠腹腔注射前体药物5-Fc+GCV(5-Fc 500mg/kg+GCV 30mg/kg),连续给药15d,每天测量1次皮下移植瘤长径和短径,计算体积。末次给药后3d处死裸小鼠,取皮下移植瘤组织做HE染色,并提取组织RNA,用RT-PCR检测CDTK的表达。结果:未转染组裸小鼠8只成瘤,转染组裸小鼠7只成瘤。两组比较,转染组皮下移植瘤的体积较未转染组小,有统计学差异(P<0.05);转染组瘤组织HE染色中可见散在坏死组织。转染组皮下移植瘤组织中检测到403bp片段,与CDTK预期mRNA大小一致。结论:双自杀基因载体pc-ChCDTK系统对裸小鼠的视网膜母细胞瘤皮下移植瘤的生长有抑制作用。

AIM:To investigate the killing effects of tumor cells specific vector of suicide gene of CDglyTK driven by hTERT promoter on retinoblastoma Y79 in vivo. METHODS:The BALB/C nude mice were devided into two groups,ten mice each.The experimental mice were injected subcutaneously with the CDTK expressional retinoblastoma Y79 cells.The control mice were injected with non-transfected Y79 cells.Intraperitoneal injections with 5-FC and GCV were started 7 days after tumor injection.Tumor was allowed to grow and established.All the mice with tumor received prodrug once per day for 15 days.The volume of tumor were observed.Furthermore, the pathological results of tumor was observed.At the same time,RT-PCR was used to detect CDTK amplification fragements in the tumors. RESULTS:The volume of the tumor in experimental group,compared to the control group,showed a significant decrease.There was significant difference in the tumor volume between the two groups(P<0.05). There was generous necrosis in the transfected group.The result of RT-PCR showed 403bp fragment that was eaqual to the expection. CONCLUSION:Tumor cells specific vector of suicide gene of CDglyTK and prodrugs can inhibit the growth of tumor of Y79 subcutaneously.