The inhibitory effect of endostar combined with radiotheraphy on gastric transplantation tumorinmice
10.3760/cma.j.issn.0254-5098.2017.03.005
- VernacularTitle:重组人内皮抑素联合放疗对小鼠胃癌移植瘤的生长抑制作用及机制的研究
- Author:
Ye TAN
;
Xiaojun WANG
;
Meiling LI
;
Haijun LU
- Keywords:
Recombinant human endostatin;
Radiotherapy;
Microvessel density;
G-protein signaling 5;
Hypoxia-induced facter-1 α
- From:
Chinese Journal of Radiological Medicine and Protection
2017;37(3):187-192
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effect of endostatin(Endostar) combined with radiotheraphy on the growth,microvessel density (MVD),the expressions of regulators of G-protein signaling 5 (RGSS),vascular endothelial growth factor (VEGF) and hypoxia-induced factor-1 α (HIF-1 α) ingastric transplantation tumor,and to explore underlying mechanism.Methods Thirty-two tumor-bearing mice were randomly divided into four groups including control group,ES group,RT group and ES + RT group.Then the tumor-bearing mice survival and tumor volume alterations were observed.After treatments of drug and RT,the inhibition rate of tumor growth and tumor MVD were measured.Immunohistochemical staining method was used to detect the expressions of RGS5,VEGF and HIF-1α.Results Compared with the ES group and control group,the ES + RT and RT treatment had effective anti-tumor effect(t=7.4,5.6,P < 0.05),where as the ES + RT was more obvious in anti-tumor with the lowest value of MVD in tumor.Compared with the control group,the expression of HIF-1α in ES group,RT group,and especially ES + RT group was significantly reduced (t =6.5,8.2,13.1,P < 0.05).The expression levels of VEGF and RGS5 wereincreased in RT group but was reduced in ES group and ES + RT group,and the expressions of VEGF and RGS5 in ES group and ES + RT group had no significant difference (P > 0.05).Rank correlation analysis showed the expression of HIF-1α and the expressions of VEGF and RGS5 were positively correlated (r =0.57,0.71,P < 0.05).Conclusions A possible mechanism of Endostar combined with radiotherapy on tumor growth inhibition may due to the inhibition of HIF-1α and its downstream VEGF and RGS5,and then inhibit tumor angiogenesis that results in the recovery of tumor blood vessels and tumor oxygen supplement.