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In vitro gene therapy of hepatocellular carcinoma using replication-defective and tumor-specific replication-competent adenovirus carrying interleukin-12 gene
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- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF ONCOLOGY
- Issue:
- 10
- DOI:
- 10.3760/j.issn:0253-3766.2004.10.002
- Key Word:
- 基因治疗;腺病毒载体;白细胞介素12;肝肿瘤;癌,肝细胞
Abstract： 目的比较携带小鼠IL-12基因的增殖型腺病毒(CNHK200-mIL12)和非增殖型腺病毒(Adv-mIL12)对IL-12基因的表达以及对肝癌细胞的杀伤能力.方法通过MTT以及病毒增殖实验,评估E1B-55 000缺陷的增殖型腺病毒CNHK200-mIL12和ONYX-015(dl1520),以及非增殖型腺病毒Adv-mIL12对人正常肝细胞株LO2、人肝癌细胞株HepG2和Hep3B的杀伤能力.采用蛋白质印迹分析和ELISA法,检测CNHK200-mIL12和Adv-mIL12感染HepG2和Hep3B细胞后,小鼠IL-12基因的表达情况.结果 CNHK200-mIL12感染HepG2和Hep3B细胞后大量增殖,在感染后96h时检测,分别增殖3160倍和630倍,在极低的MOI(空斑形成单位/细胞)值和极短的时间内(HepG2细胞:MOI=0.2,第4天;Hep3B细胞:MOI=0.005,第2天),可大量杀伤肿瘤细胞,而对LO2细胞无明显杀伤.CNHK200-mIL12和Adv-mIL12感染HepG2细胞后,其IL-12基因表达量,前者是后者的101倍;感染Hep3B细胞后,前者是后者的20倍.结论增殖型腺病毒载体对肿瘤细胞的杀伤能力和目的基因的表达,明显优于传统的非增殖型腺病毒载体,应用前景广阔.
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