Abstract
Angiogenesis is tightly held together with the further development of solid tumors, and antiangiogenic therapy remains highly exceptional promise as an inhibitor in several cancer-related diseases. In this study, the gene encoding human endostatin and angiostain fusion protein (hEA) was directly delivered to tumor cells by baculoviral vectors combined with Sleeping Beauty (SB) transposon system for long-term inhibition of tumor-induced angiogenesis. We first constructed three recombinant baculoviruses: Bac-hEA/w harboring the hEA gene under the transcriptional control of cytomegalovirus immediate-early (CMV-IE) promoter and the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) inserted into downstream of hEA gene to enhance the expression of therapeutic protein, Bac-SB-T2-hEA/w harboring the same gene expression cassette flanked by inverted repeats (IR) as a whole SB transposon and the expression cassette of SB tansposase (i.e. in cis), and Bac-SB-T2-luc/w with luciferase gene substituting for hEA gene of Bac-SB-T2-hEA/w. In animal studies, baculoviral vectors themselves showed marked anti-tumor effect without reduction of tumor vessel density in early days after virus injection, and long-term expression of hEA demonstrated decrease in tumor-induced angiogenesis (p < 0.05) and consequently retarded the tumor growth more effectively.