Endostatin Gene Therapy for Endometriosis in Rats

Abstract

Endostatin gene therapy for endometriosis was studied in an experimental autotransplantation model in rats. Endometriotic lesions were transfected by intralesional injection of the plasmid lipofectamine-endostatin-pBud (group 1), lipofectamine-pBud (empty vector; group 2) or phosphate-buffered saline (group 3). Endostatin mRNA and protein levels in lesions were evaluated by quantitative real-time reverse transcription-polymerase chain reaction and Western blot analysis. Endostatin and vascular endothelial growth factor (VEGF) protein levels in serum, and microvessel density (MVD) and matrix metalloproteinase (MMP)-2 protein levels in endometriotic lesions, were also determined. Lipofectamine-endostatin-pBud injection increased endostatin mRNA and protein levels in lesions. Lesions were significantly smaller, and serum VEGF levels significantly lower, in group 1 versus controls. Serum VEGF was significantly and negatively correlated with serum endostatin. In group 1, MMP-2 levels and MVD were significantly lower versus controls. MMP-2 level was negatively correlated with endostatin. Gene therapy with endostatin appears to be an effective treatment for endometriosis. Restoration of endostatin gene expression by gene transfer in vivo might be a potential gene therapy approach for human endometriosis.