Effects of endostatin on C6 glioma-induced edema.
- Author:
Li-Juan YANG
1
;
Zhi-Xiong LIN
;
De-Zhi KANG
;
Shen-Mei WENG
;
Jian-Hua LIN
;
Qiang HUANG
;
Peng-Fei ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Cell Line, Tumor; Edema; drug therapy; etiology; Endostatins; therapeutic use; Enzyme-Linked Immunosorbent Assay; Glioma; drug therapy; physiopathology; Male; Mice; Mice, Inbred BALB C; Polymerase Chain Reaction; Rats; Xenograft Model Antitumor Assays
- From: Chinese Medical Journal 2011;124(24):4211-4216
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDGlioma-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.
METHODSTumorigenic 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.
RESULTSOverexpression 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.
CONCLUSIONSOur data provide primary evidence that endostatin reduces glioma-induced edema and vascular permeability. Using endostatin may be an effective strategy for treating glioma edema.