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利用CEA(癌胚抗原)只在肺腺癌中表达,而不在正常肺组织中表达的特点,构建了由CEA启动子控制的单纯疱疹病毒胸苷激酶基因(HSV-TK)的逆转病毒载体(pCEATK),然后将pCEATK导入表达CEA的人肺腺癌细胞GL和不表达CEA的HeLa细胞,在体内外观察了Ganciclovir(GCV)的治疗效果和“旁观者效应”.结果表明pCEATK只在表达CEA的肺腺癌GL细胞中特异表达,而不在HeLa细胞表达;GL的pCEATK转染细胞对GCV的敏感性增加了992倍,在裸鼠体内GCV也可以明显抑制GL转染细胞的生长,并有明显的“旁观者效应”现象;而HeLa的pCEATK转染细胞体内外对GCV的敏感性没有明显变化.这提示由CEA启动子控制的HSV-TK的逆转病毒载体对表达CEA的人肺腺癌的基因治疗可能是治疗人肺腺癌的有效方法.
Using CEA (Carcinoembryonic Antigen) expression in lung adenocarcinoma but not in normal lung tissue, a retroviral vector for the herpes simplex virus thymidine kinase gene (HSV-TK) controlled by the CEA promoter was constructed. pCEATK), then pCEATK was introduced into CEA-expressing human lung adenocarcinoma cells GL and HeLa cells not expressing CEA. The therapeutic effect and “bystander effect” of Ganciclovir (GCV) were observed in vitro and in vivo. The results showed that pCEATK only expressed CEA. The specific expression of lung adenocarcinoma GL cells, but not in HeLa cells; GL pCEATK transfected cells sensitivity to GCV increased by 992 times, GCV in nude mice can also significantly inhibit the growth of GL transfected cells, and Obvious “bystander effect” phenomenon; while HeLa’s pCEATK transfected cells did not show significant changes in GCV sensitivity in vivo and in vitro. This suggests that the reversal of HSV-TK by the CEA promoter reverses viral vectors against human lung adenocarcinoma expressing CEA. Gene therapy may be an effective method to treat human lung adenocarcinoma.