Novel cancer gene therapy using apoptosis-related gene

Caspase-3是半胱氨酸蛋白酶家族的成员，在细胞凋亡中起重要作用。我们将人caspase-3基因作为一种新的抗癌基因治疗形式。单独过表达人caspase-3不能诱导肿瘤细胞凋亡，而加入VP-16可显著促进肿瘤细胞凋亡。在AH 13 O肝癌模型中，转染人caspase-3，而空载体与VP-16联合应用时，可诱导广泛的细胞凋亡和缩小肿瘤体积，但对Bcl-2过表达的肿瘤没有观察到这些作用。

Caspase-3 is a member of the cysteine protease family, which plays a crucial role in apoptosis.We applied the human caspase-3 gene as a novel form of anticancer gene therapy.Overexpression of human caspase-3 alone could not induce apoptosis of tumor cell lines, whereas apoptosis was markedly enhanced by the addition of VP-16.In an AH13O liver tumor model, transfection of human caspase-3, but not the empty vector, induced extensive apoptosis and reduced tumor volume, when applied together with VP-16.However, these effect was not observed with a Bcl-2 overexpressing tumor.In conclusion, caspase-3 gene transfection accompanied by an additional death stimulus may be useful anticancer gene therapy, except for Bcl-2 overexpressing tumors.