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目的 通过动物实验初步筛选对肝癌有明确疗效的目的基因。方法 应用携带对肿瘤有明确疗效的目的基因白细胞介素 2 (interleukin 2 ,IL 2 )、白细胞介素 12 (interleukin 12 ,IL 12 )、共刺激因子B7 1(costimulatorB7 1,B7 1)、单纯疱疹病毒胸苷激酶 (herpessimplex 1thymidinekinase ,HSV TK)、抑癌基因p5 3及白细胞介素 1β转换酶 (interleukin 1βconvertingenzyme,ICE)的逆转录病毒包装细胞系PA317,将该包装细胞系与肝癌细胞CBRH3 混合接种于大鼠腹腔中。结果 生理盐水及病毒载体对照组大鼠的平均生存时间分别为 (8 2± 0 8)及 (8 3± 1 1)d ,IL 2、B7 1、HSV TK、p5 3及ICE治疗组大鼠的平均生存时间分别为 (15 8± 2 4)、(10 6± 1 8)、(15 5± 2 5 )、(15 1± 2 5 )、(16 3± 2 0 )d ,生存期明显延长。IL 12治疗组的大鼠均存活超过 2个月。携带IL 12的逆转录病毒包装细胞株与CBRH3 的比例超过 1∶10时可使大鼠长期生存 (2个月观察期 ) ,而低于 1∶10 0时大鼠平均生存时间为(14 6± 2 1)d。结论 应用IL 12目的基因对肝癌的疗效最为显著。携带IL 12的逆转录病毒包装细胞株通过激活机体免疫细胞可完全杀灭超过其 10倍的肝癌细胞。
Objective To screen the target genes that have a clear effect on liver cancer through animal experiments. Methods The target genes interleukin 2 (IL 2), interleukin 12 (IL 12), costimulator B7 1, B7 1, and herpes simplex were used to carry specific therapeutic effects on tumors. The retroviral packaging cell line PA317 of viral thymidine kinase (HSV TK), tumor suppressor gene p53, and interleukin 1β converting enzyme (ICE) was used to inoculate the packaging cell line with hepatoma cell CBRH3. In the abdominal cavity of rats. Results The average survival time of normal saline and virus vector control group rats were (8 2 ± 0 8) and (8 3 ± 11) d, IL 2, B7 1, HSV TK, p 5 3 and ICE treatment group rats. The average survival time was (15 8±24), (10 6±18), (15 5±25), (15 1±25), (16 3±20)d, and the survival time was obvious. extend. Rats in the IL 12 treatment group survived for more than 2 months. The ratio of retroviral packaging cell strains carrying IL 12 to CBRH3 exceeding 1 : 10 allows long-term survival in rats (observation period of 2 months), while the average survival time in rats below 1:10 0 (14 6). ± 2 1)d. Conclusion The application of IL 12 gene is most effective in liver cancer. The retroviral packaging cell line carrying IL 12 completely kills liver cancer cells exceeding 10 times by activating immune cells.