Antiangiogenesis gene therapy for advanced hepatocellular carcinoma by transferrin-DNA conjugate.

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Advanced hepatocellular carcinoma (HCC) is one of poor prognostic malignancies. As an alternative therapy to overcome these malignancies, we have developped the novel gene therapy with systemic administaration of Transferrin-DNA conjugate for disseminated lesions. Here we extended this system to the anti-angiogenesis gene therapy because it is well known that advanced HCC is hypervascular tumor and the blood supply is definitely dependent on the arterial blood flow. Angiostatin (Ast) is one of the potent antiangeogenesis factor and induces the apoptosis in vascular endotherial cells (Endt). However the little of the mechanism of apoptosis is elucidated yet. The aim of this study is to examine whether caspase and reactive oxygene species (ROS) are involved in the apoptotic process of Endt by Ast. Anti-oxydant agent significantly inhibited apoptosis of CPAE cells induced by Ast. Caspase 3 inhibitor also inhibited apoptosis of CPAE cells induced by Ast. These results demonstrate that caspase 3 and ROS are involved in the process of apoptosis induced by Ast.