Effects of endostatin on C6 glioma-induced edema

• Published in: Chinese medical journal Vol. 124; no. 24; pp. 4211 - 4216
• Main Authors: Yang, Li-Juan, Lin, Zhi-Xiong, Kang, De-Zhi, Weng, Shen-Mei, Lin, Jian-Hua, Huang, Qiang, Zhang, Peng-Fei
• Format: Journal Article
• Language: English
• Published: China Department of Pharmacology , Fujian Medical University, Fuzhou, Fujian 350005, China%Department of Neurosurgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, China%Laboratory of Tumorous Invasion Microecosystem , Fujian Medical University, Fuzhou, Fujian 350005, China%Department of Neurosurgery, the Second Hospital, Suzhou University, Suzhou, Jiangsu 215004, China%Department of Pathology , Fujian Medical University, Fuzhou, Fujian 350005, China 20.12.2011
• Subjects: Animals; Cell Line, Tumor; Edema - drug therapy; Edema - etiology; Endostatins - therapeutic use; Enzyme-Linked Immunosorbent Assay; Glioma - drug therapy; Glioma - physiopathology; Male; Mice; Mice, Inbred BALB C; Polymerase Chain Reaction; Rats; Western印迹; Xenograft Model Antitumor Assays; 单向方差分析; 抑制素; 水肿; 脑胶质瘤; 血管内皮细胞; 血管通透性; 酶联免疫吸附试验; glioma; edema; endostatin; vascular endothelial growth factor; angiogenesis
• ISSN: 0366-6999; 2542-5641
• DOI: 10.3760/cma.j.issn.0366-6999.2011.24.017

Background 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. Methods 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. Results 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. Conclusions 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.