Egr-IFNγ基因治疗联合125I-脱氧尿嘧啶核苷治疗抑瘤效应的实验研究

目的 探讨Egr-IFNγ基因治疗联合放射性核素 ¹²⁵I -脱氧尿嘧啶核苷治疗方案在荷H22肝癌细胞小鼠体内抑瘤效应及机制。方法 小鼠肿瘤局部注射脂质体包裹的质粒,注射后48 h,肿瘤局部注射370kBq ¹²⁵I -UdR。观察各组小鼠治疗后不同时间肿瘤生长率;治疗后第3 天,检测肿瘤胞浆蛋白中IFNγ的表达和脾脏CTL细胞毒活性。结果 基因-放射核素治疗后第6～15天,pcDNAEgr-IFNγ+ ¹²⁵I -UdR组肿瘤生长率明显低于对照组、 ¹²⁵I -UdR组及pcDNAEgr-1+ ¹²⁵I -UdR 组;基因-放射性核素治疗后第3天,pcDNAEgr-IFNγ+ ¹²⁵I -UdR组肿瘤胞浆蛋白中可检测到IFNγ的表达,其余组肿瘤胞浆蛋白中未检测到IFNγ的表达;pcDNAEgr-IFNγ+ ¹²⁵I -UdR组小鼠脾脏CTL细胞毒活性明显高于其余组 (P<0.01)。结论 pcDNAEgr-IFNγ基因治疗联合放射性核素 ¹²⁵I -UdR治疗抑瘤效应明显优于单纯 ¹²⁵I -UdR放射性核素治疗。

Anti-tumor effects of Egr-IFNγ gene therapy combined with 125I-UdR radionuclide therapy

Objective To explore the anti-tumor effects of Egr-IFNγ gene therapy combined with 125I-UdR radionuclide therapy in mice bearing H22 hepatocarcinoma and its mechanism. Methods The recombinant plasmid pcDNAEgr-IFNγ mixed with liposome was injected into tumor. 48 h later, 370 kBq 125I-UdR was injected into tumor. The tumor growth rates at different times were observed. After 3 d gene-radionuclide therapy, the concentration of IFNγ in cytoplasm of H22 cells and cytotoxic activities of splenic CTL of the mice in different groups were examined. Results The tumor growth rates of pcDNAEgr-IFNγ +125 I-UdR group were obviously lower than those of control group, 125I-UdR group and pcDNAEgr-1 +125I-UdR group 6-15 d after gene-radionuclide therapy. IFNγ protein was found in cytoplasm of H22 cells in PcDNAEgr-1FNγ+125I-UdR group after 3 d gene-radionuclide therapy. Cytotoxic activity of splenic CTL in pcDNAEgr-IFN7 + 125I-UdR group was significantly higher than that in the other groups (P<0.01). Conclusions The anti-tumor effects in vivo of pcDNAEgr-IFNγ gene therapy combined with 125I-UdR radionuclide therapy are better than those of 125I-UdR therapy.