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目的 :研究携带小鼠白细胞介素 12 (m IL- 12 )和人白细胞介素 2 (h IL- 2 )基因的逆转录病毒包装细胞株对大鼠肝癌进行联合基因治疗的可行性和疗效。 方法 :构建携带 m IL- 12基因、h IL- 2基因及 m IL- 12 +h IL- 2基因的逆转录病毒包装细胞PA317- GCIL12 EXPN、PA317- GCXEIL2 PN和 PA317- GCIL12 EIL2 PN,分别与肝癌细胞 CBRH3以 1∶ 1混合接种于大鼠腹腔。观察其生存时间。 结果 :生理盐水对照组、空载体对照组 (PA317- GCXEXPN)和 h IL - 2治疗组的平均生存时间分别为(8.5± 1.2 ) d、(8.3± 0 .9) d和 (16 .7± 1.7) d;m IL - 12治疗组和 m IL - 12 +h IL - 2治疗组均长期存活。逆转录病毒包装细胞与CBRH3的比例为 1∶ 10 0混合时 ,m IL - 12 +h IL - 2治疗组仍能长期存活 ,而 m IL - 12治疗组平均生存时间为 (15 .7± 1.8) d。腹腔接种 CBRH3后 1、3、5、7d,采用 m IL- 12 +h IL- 2治疗后 35 d生存率分别为 10 0 %、10 0 %、30 %、15 %。 结论 :携带 m IL- 12和 h IL - 2基因的逆转录包装细胞株可明显抑制肝癌细胞的生长 ,早期治疗优于晚期治疗 ,联合基因治疗比单基因治疗更有效
Objective: To investigate the feasibility and efficacy of combined gene therapy in retroviral packaging cell lines carrying murine interleukin-12 (IL-12) and human interleukin-2 (IL-2) genes. METHODS: The retroviral packaging cells PA317-GCIL12 EXPN, PA317-GCXEIL2 PN and PA317-GCIL12 EIL2 PN carrying m IL-12 gene, h IL-2 gene and m IL-12 + h IL- Hepatocellular carcinoma cells CBRH3 were inoculated 1: 1 into the abdominal cavity of rats. Observe the survival time. Results: The average survival time in the saline control group, empty vector control group (PA317-GCXEXPN) and hIL - 2 treatment group were (8.5 ± 1.2) d, (8.3 ± 0.9) d and (16.7 ± 1.7) d; m IL - 12 treatment group and m IL - 12 + h IL - 2 treatment group were long - term survival. When the ratio of retroviral packaging cells to CBRH3 was 1:10, the mIL - 12 + hIL - 2 treatment group could still survive for a long time, while the mean survival time of the mIL - 12 treatment group was (15.7 ± 1.8) d. After 1,3,5,7 d CBRH3 was administered intraperitoneally, the 35-day survival rates after treatment with m IL-12 + h IL-2 were 100%, 100%, 30% and 15%, respectively. CONCLUSIONS: The retroviral packaging cell lines harboring m IL-12 and hIL-2 genes can significantly inhibit the growth of hepatocellular carcinoma cells. The early treatment is superior to the late treatment, and the combined gene therapy is more effective than the single-gene therapy