Combined targeting of interleukin‐6 and vascular endothelial growth factor potently inhibits glioma growth and invasiveness

摘要: Interleukin-6 (IL6) and vascular endothelial growth factor (VEGFA) are abundantly produced by glioma cells contribute to malignancy promoting angiogenesis, cell proliferation resistance apoptosis. We compared the effect of inhibiting IL6 VEGF on U87-derived experimental grown chick chorio-allantoic membrane (CAM) or in brain xenografted mice. Tumor was monitored biomicroscopy immunohistology. In vitro, knockdown had no but substantially enhanced invasion. CAM glioma, reduced vascularization tumors with a comparable efficiency, increased invasion residual tumor cells. contrast, combined IL6/VEGF not only showed reduction angiogenesis also significantly prevented mice, combining Avastin TM treatment completely abrogated development infiltration. Molecular response single studied transcriptomic profiling. Many cycle genes chromatin components were silenced double knockdown. addition, specific migratory signatures detected under partially erased tumors. Our results show that combination inhibitors brings synergistic antitumoral benefit reduces global activity major pathways survival, invasiveness remaining may be induced using alone. ' 2009 UICC