Recombined adeno-associated viral vector-mediated systemic delivery of caveolin-1 inhibits angiogenesis of implanted hepatocellular tumor in vivo / 中华普通外科杂志

ABSTRACT

Objective To investigate the antitumor effect of the recombined adeno-associated virus encoding caveolin-1 regulated by progression-elevated gene (PEG) promotor on the angiogenesis of implanted human hepatocellular carcinoma(HCC) cell lines in a nude mouse model. Methods HepG2 cells were inoculated subcutaneously into NOD/SCID mice, and animals were treated with rAAV-PEG-caveolin-1 after tumor cell innoculation. The fluorescence ratio of Evans blue to FITC-dextran was used to assess the changes of microvasculature permeability of the tumor. Western blot and immunohistochemical analyses were employed to detect PECAM-1 expression in tumor microvascular endothelium and microvessel density(MVD), respectively; NOS activity was assessed by citrulline generation. Tumor growth was observed and tumor cell apoptosis in tumor tissues were measured by TUNEL. Results Tumor growth was significantly inhibited in mice injected with rAAV-PEG-caveolin-1. The administration of rAAV-PEG-caveolin-1 significantly blocked vascular leakage in the tumor microcirculation. The levels of PECAM-1 protein detected by Western blot were markedly reduced in rAAV-PEG-caveolin-1-treated mice, and there were fewer MVD in tumors from caveolin-1-treated mice, while NOS catalytic activity was much lower in rAAV-PEG-caveolin-1-treated mice compared to the control and empty vector-treated animals. TUNEL demonstrated significant induction of tumor cell specific apoptosis. Conclusions rAAV-PEG-caveolin-1 can reduce tumor progression through blocking microvascular formation by inhibiting eNOS.