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[贝伐单抗对胃癌异种移植瘤中血管内皮生长因子及Sp1表达的影响]

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

作者信息

Zhou Chen-fei, Ji Jun, Yuan Fei, Yu Ying-yan, Liu Bing-ya, Zhang Jun, Zhu Zheng-gang

机构信息

Department of Surgery, Shanghai Jiaotong University School of Medicine, Shanghai, China.

出版信息

Zhonghua Wei Chang Wai Ke Za Zhi. 2012 Feb;15(2):180-4.

PMID:22368029
Abstract

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 microvessel 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.

摘要

目的

评估贝伐单抗对胃癌异种移植瘤生长、增殖和凋亡的影响,以及对血管内皮生长因子(VEGF)和特异性蛋白1(Sp1)表达的影响。

方法

采用SGC-7901胃癌细胞系建立裸鼠胃癌异种移植瘤模型。将裸鼠随机分为两组,即贝伐单抗治疗组和磷酸盐缓冲液(PBS)组。测量肿瘤大小以绘制肿瘤生长曲线。通过免疫组织化学(IHC)染色检测Ki67和CD34评估增殖和血管生成情况。采用末端脱氧核苷酸转移酶介导的缺口末端标记法(TUNEL)检测凋亡情况。通过IHC和蛋白质免疫印迹法检测肿瘤细胞中VEGF和Sp1的表达。

结果

与PBS组相比,贝伐单抗组肿瘤生长显著减缓(P<0.05),肿瘤细胞增殖和血管生成减少,凋亡指数显著增加[(5.3±1.8)%对('16.7±6.7)%,P<0.01]。IHC和蛋白质免疫印迹法结果显示,贝伐单抗治疗组VEGF表达和微血管密度(MVD)降低(4.0±1.0对16.3±1.5,P<0.001)。贝伐单抗治疗组未观察到Sp1表达有明显变化。

结论

贝伐单抗可抑制裸鼠胃癌异种移植瘤生长,降低VEGF表达和MVD。然而,转录因子Sp1的代偿性上调不受贝伐单抗影响。

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