贝伐单抗对裸鼠胃癌移植瘤血管内皮细胞生长因子和核转录因子Sp1表达的影响

Impacts of Bevacizumab on vascular endothelial growth factor and Sp1 expression in gastric cancer xenografts

目的 观察贝伐单抗对裸鼠胃癌移植瘤生长以及对肿瘤血管内皮细胞生长因子（VEGF）和核转录因子Sp1表达的影响.方法 建立SGC-7901胃癌细胞株裸鼠移植瘤模型,成瘤后分别使用贝伐单抗（BVZ组）和磷酸盐缓冲液（PBS组）治疗4周.绘制肿瘤生长曲线,免疫组织化学染色技术（IHC）检测移植瘤Ki-67、CD34、VEGF及Sp1表达情况,TUNEL法检测肿瘤细胞凋亡.结果 相比PBS组,BVZ组肿瘤生长速度明显减缓（P〈0.05）,肿瘤细胞增殖能力下降,凋亡指数明显增加[（5.3±1.8）％比（16.7±6.7）％,P＜0.01],肿瘤组织内微血管密度下降（4.0±1.0比16.3±1.5,P＜0.001）.贝伐单抗能减少肿瘤内VEGF表达,但对核转录因子Sp1表达水平没有明显影响.结论 贝伐单抗可有效抑制裸鼠胃癌移植瘤生长,减少肿瘤内微血管密度和VEGF表达,但不引起Sp1表达的明显改变.

Objective To evaluate the effects of Bevacizumab on the tumor growth,proliferation and apoptosis of gastric cancer xenograft, and the impacts on the VEGF and Sp1 expression.Methods Gastric cancer xenografts in nude mice were established using SGC-7901 gastric cancer cell line.The nude mice were randomly divided into two groups,Bevacizumab treatment group and PBS group.The tumor sizes were measured for tumor growth curve.The proliferation and angiogenesis were evaluated by immunohistochemistry （IHC） staining of Ki67 and CD34.TUNEL assay was used for apoptosis evaluation.The expression of VEGF and Sp1 in tumor cells were detected by IHC and Western blot.Results Compared to the PBS group,the tumor growth decreased significantly （P〈0.05）, the proliferation of tumor cells and angiogenesis decreased,and apoptosis index increased significantly [ （5.3±1.8）% vs.（16.7 ±6.7）%,P〈0.01 ] in Bevacizumab group.The results of IHC and Western blot demonstrated that the expression of VEGF and the mircovessel density （MVD） was decreased （4.0± 1.0 vs.16.3±1.5,P〈0.001） in Bevacizumab treatment group.No obvious changes of Sp1 expression were observed in Bevacizumab treatment group.Conclusions Bevacizumab can inhibit the growth of gastric cancer xenografts in nude mice,decrease the VEGF expression and MVD.However,the compensatory up-regulation of transcription factor Sp1 is not affected by Bevacizumab.