Effects of endostatin on C6 glioma-induced edema / 中华医学杂志(英文版)

ABSTRACT

<p><b>BACKGROUND</b>Glioma-induced edema is considered as one of the most pathological characteristics of glioma and a significant source of morbidity and mortality. New strategies are needed for the treatment of peritumoral edema in glioma. Endostatin has been proven to be beneficial as an anti-angiogenic agent in experimental gliomas, but the effects are unclear. This study aimed to investigate the effects of endostatin on C6 glioma-induced edema.</p><p><b>METHODS</b>Tumorigenic mice were established by subcutaneous injection of three glioma cell lines, C6-null cells and stable transfected-C6 cells overexpressing mock vector (C6-mock cells) and endostatin (C6-endo cells). Endostatin expression in xenograft C6 glioma was determined by immunostaining and Western blotting. Glioma-induced edema and tumor vessel permeability were assayed. The effect of endostatin on vascular enodothelial growth factor (VEGF) expression in vivo was analyzed by quantitative polymerase chain reaction (Q-PCR) and enzyme-linked immunosorbent assay (ELISA). The number of vesiculo-vascuolar organelles (VVOs) formed in tumor endothelia was calculated using electron microscopy. Data were analyzed by using one-way analysis of variance (ANOVA) followed by Dunnett's post hoc test for multiple comparisons to the control groups.</p><p><b>RESULTS</b>Overexpression of endostatin (C6-endo cells) significantly suppressed tumor growth and reduced tumor edema and vessel permeability. ELISA analysis showed that the level of VEGF protein was markedly decreased in tumor from C6-endo cells compared with tumor from C6-null cells and C6-mock cells. Similar results were obtained by Q-PCR. Furthermore, the number of VVOs observed in tumor from C6-endo mice was significantly reduced compared with tumor from C6-null cells or C6-mock cells.</p><p><b>CONCLUSIONS</b>Our data provide primary evidence that endostatin reduces glioma-induced edema and vascular permeability. Using endostatin may be an effective strategy for treating glioma edema.</p>