| Objective: Tumor growth is a vessel-dependent process. Anti-angiogenesis therapy has been an important treatment of cancer therapy. Endostatin, the C-terminal proteolytic fragment, of collagenⅩⅧ, is a potent endogenous vascular inhibitor. In this study we made a research of whether intraveinous administration recombinant human Endostatin adenovirus complex with cationic liposome vector would inhibit angiogenesis and the growth of ovarian cancer in the nude mice, and evaluate the effects of liposome plus Ad-Endostatin complex on Human ovarian serous cystocarcinoma.Method: We investigated the expression of recombinant endostatin protein in SKOV3 cells, transfected with constructed recombinant adenovirus. The nude mice animal models which with Human ovarian serous cystocarcinoma were established with SKOV3 cells, nude mice were randomly divided into six groups: (1) Ad-hEndo-H plus liposome group (abbreviation:lipo+Ad-hEndo-H), i.v. administration of 1×109 pfu(plaque-forming units) recombinant adenovirus +200μg liposome (n=5), (2) Ad-hEndo-L plus liposome group (abbreviation: lipo+Ad-hEndo-L), i.v. administration of 1×108 pfu recombinant adenovirus +20μg liposome (n=5), (3) Ad-hEndo group, i.v. administration of 1×109 pfu recombinant adenovirus (n=4); (4) Ad-null plus liposome group, i.v. administration of 1×109 pfu +200μg liposome(n=4), (5) liposome group, i.v. administration liposome for 200μg (n=4); And (6) NS group (n=4), equal volume of normal saline on the same schedule as above. All of the treatments single. Tumor growth was monitored by periodic caliper measurements every 7 days. Nude mice in all groups were sacrificed 49 days after tumor establishment, and tumors were removed weighted. Immunohistochemistry and TUNEL assay in tumor section. The micro-vessel density (MVD) was counted then measured the numbers of apoptotic cells in the tumors areas by TUNEL assays.Results: Our data demonstrated the treatment with liposome-complexed adenovirus significantly reduced the formation of microvascular angiogenesis in tumor tissue, treatment with the complexes caused very significant tumor volume reduction. Lipo+null and Ad-hEndo caused less reduction of tumor weight 39.48% and 38.81% respectively, whereas treatment with lipo+Ad-hEndo-L and lipo+Ad-hEndo-H caused very significant tumor weight reduction 70.65% and 54.74%. These MVD data indicate that lipo+Ad-hEndo-L and lipo+Ad-hEndo-H treated tumors decreased the density of blood vessels. While the number of apoptotic cells in the Ad-hEndo treated group was significantly higher than in the NS group or other groups. More importantly the complex with adenoviral and liposome further increased the number of apoptotic cells compared with the Ad-hEndo alone.Conclusions: These data suggested that liposome-complexed adenoviral delivery of genes encoding endostatin may represent a potentially new treatment for Human ovarian serous cystocarcinoma with complex, it may be possible not only to facilitate expression of therapeutic genes but also to deliver a lower titer of adenoviral vector and as a result reduce toxicity and immunogenicity in vivo.
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