贝伐单抗对乳腺癌皮下移植瘤放疗的增敏作用及其机制

Effect and mechanisms of bevacizumab in breast cancer xenograft radiotherapy model

目的 观察贝伐单抗对乳腺癌皮下移植瘤放射治疗的影响并探讨其机制.方法 将30只建立皮下移植瘤裸鼠随机分为贝伐单抗联合放射治疗组、单纯放射治疗组、正常组,相应处理后绘制生长曲线,Western blot法及免疫组织化学法检测各组缺氧诱导因子（HIF）-1α、血管内皮生长因子（VEGF）、细胞核增殖抗原（Ki-67）、CD31的表达.结果 联合组皮下移植瘤退缩更为显著（P＜0.05）；免疫组织化学显示联合组Ki-67表达最弱,HIF-1 α、CD31表达也较单纯放射治疗组减弱,差异有统计学意义（P＜0.05）；Western blot显示联合组HIF-1α、VEGF表达最弱.结论 贝伐单抗在乳腺癌皮下移植瘤放射治疗中发挥放射治疗增敏作用,可能是通过抑制HIF-1α、VEGF表达从而抑制肿瘤细胞增殖及肿瘤组织内血管形成来实现的.

Objective To observe the radiosensiti.zing activity of bevacizumab on breast cancer xenograft model,and to explore its possible mechanisms.Methods Thirty mice with subcutaneous transplantation tumor were randomly divided into group of bevacizumab in combination with radiotherapy,radiotherapy alone group and normal control group,and the effect of bevacizumab on breast cancer xenograft was studied.By using Western blotting and immunohistochemistry,the expression of hypoxia-inducible factor-1α （HIF-1o）,vascular endothelial growth factor （VEGF）,proliferating cell nuclear antigen （Ki-67）,and platelet and endothelial cell adhesion molecule （CD31） was detected in tumor tissues.Results The subcutaneous xenograft in combination group was decreased significantly as compared with radiotherapy alone group （P ＜ 0.05）.Immunohistochemistry revealed that combination group expressed the weakest set of Ki-67,HIF-1 α and CD31 （P ＜ 0.05）.Western blotting showed that combination group also had the weakest expression of HIF-1α and VEGF.Conclusion Bevacizumab could play a role of radiosensitization in breast cancer subcutaneous transplantation tumor,which was induced by the inhibition of HIF-1 o,VEGF expression and suppression of tumor cell proliferation and angiogenesis.