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人干扰素α2基因经电穿孔递送后的基因表达及抗肿瘤作用

Gene expression and antitumor effect following im electroporation delivery of human interferon alpha 2 gene.

作者信息

Zhang Guo-Hua, Tan Xiao-Fan, Shen Dong, Zhao Shu-Yuan, Shi Yan-Li, Jin Cai-Ke, Sun Wei-Gu, Guo Yan-Hong, Chen Kuang-Hueih, Tang Jian

机构信息

Institute of Cardivascular Basic Research, Peking University Health Science Center, Beijing 100083, China.

出版信息

Acta Pharmacol Sin. 2003 Sep;24(9):891-6.

PMID:12956937
Abstract

AIM

To investigate the gene expression and antitumor effect following im electroporation delivery of human interferon alpha 2 (hIFN-alpha 2) gene.

METHODS

The pcD2/hIFN-alpha 2 was injected into the middle of the quadriceps muscle of female BALB/c mice or the leukemia-bearing female BALB/c nude mice, and then electroporation was given to the injection site. Optimal electrical parameters and the efficiency of gene transfer was studied with hIFN-alpha 2 ELISA kit. The HL-60 tumor model in BALB/c nude mice was used to investigate therapeutic effects of im electroporation delivery of pcD2/hIFN-alpha 2.

RESULTS

The optimal conditions for the electric pulses were as follows: voltage at 200 V/cm; pulse duration at 40 ms per pulse; number of pulse at 6 pulses and frequency at 1 Hz. Under optimal conditions, the serum hIFN-alpha 2 levels in electroporation group (160 microg/L+/-31 microg/L) were 45-fold higher than those of nonelectroporation group (3.6 microg/L+/-1.6 microg/L, P<0.01). The growth of leukemia was inhibited more obviously and the survival time of the leukemia-bearing nude mice was prolonged after im electroporation delivery of pcD2/hIFN-alpha 2 100 microg or 200 microg.

CONCLUSION

Electroporation was an efficient method for the delivery of plasmid DNA and im electroporation delivery of pcD2/hIFN-alpha 2 was effective in treating leukemia.

摘要

目的

研究经皮电穿孔递送人干扰素α2(hIFN-α2)基因后的基因表达及抗肿瘤作用。

方法

将pcD2/hIFN-α2注射到雌性BALB/c小鼠或荷白血病雌性BALB/c裸鼠股四头肌中部,然后对注射部位进行电穿孔。用hIFN-α2 ELISA试剂盒研究最佳电参数和基因转移效率。利用BALB/c裸鼠的HL-60肿瘤模型研究经皮电穿孔递送pcD2/hIFN-α2的治疗效果。

结果

电脉冲的最佳条件如下:电压为200 V/cm;脉冲持续时间为每脉冲40 ms;脉冲数为6个脉冲,频率为1 Hz。在最佳条件下,电穿孔组血清hIFN-α2水平(160μg/L±31μg/L)比非电穿孔组(3.6μg/L±1.6μg/L,P<0.01)高45倍。经皮电穿孔递送100μg或200μg pcD2/hIFN-α2后,白血病的生长受到更明显的抑制,荷白血病裸鼠的生存时间延长。

结论

电穿孔是一种有效的质粒DNA递送方法,经皮电穿孔递送pcD2/hIFN-α2对白血病治疗有效。

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