Experimental study on influence of endostatin on pathological features of C_6 glioma / 中国药理学通报

ABSTRACT

Aim To investigate the influence of endostatin on pathological morphology of C_6 glioma and its molecular pharmacologic mechanism.Methods The C_6 cells,the C_6 clone stably transfected with endostatin cDNA(endo-C_6),which the endostatin with biological activities can be secreted from,and the C_6 clone stably transfected with empty vector pBudCE4.1 cDNA(pBud-C_6) were injected subcutaneous in nude mice to establish different tumoral model respectively.The morphologies of these tumoral tissues were observed and compared to each other under light and electron microscope.The expression of VEGF in tumor tissue was determined by ELISA.Results The expression of VEGF in endo-C_6 glioma(endo-C_6G) tissues was lower than that in C_6 glioma(C_6G) and pBud-C_6 glioma(pBud-C_6G).Moreover,endo-C_6G tissue was characteristic of a mimetic envelope,no intratumor bleeding and cystis degeneration,apoptosis of tumor cells,and edema in and around tumor.Rarefied vessels were found in tumor,and no vessel like structure formed by tumor cells was observed.The large irregular necrosis focus was showed in tumor,but mild vascular reaction around necrosis focus and peritumor,rare surrounding invasion.The basal lamina was discontinued.The basemembrane(BM) was loose.Few vesicular vacuolar organelle(VVO) structures were observed in plasma of endothelial cells.In C_6G and pBud-C_6G,tumor lesions demonstrated significant vascular reaction,intratumor bleeding,necrosis,edema in and around tumor,and surrounding infiltration.Vessel like structure formed by tumor cells was also observed.When examined with electron microscope,plenty of VVO structures were observed in plasma of endothelial cells,the worse the edema,the more the VVO were,which coincided with the expression of VEGF.Mostly,loose basal lamina surrounded by small amounts of collagen fibers was multilayer and integrated and continuous.No correlation between gene transfection and fenestra formation or cleft of capillary endothelial cell was observed,no apoptosis of endothelial cells were found.Conclusion In glioma,the apoptosis of endothelial cells tissue was not induced directly by endostatin,but the angiogenesis and vascular reaction can be inhibit by endostatin by down-regulation of the expression of VEGF in C_6 glioma cells.