Effects of rosiglitazone on the growth and lymphangiogenesis of human gastric cancer transplanted in nude mice

被引:16
作者
Chen, Fang-Zhi [1 ,2 ]
Mo, Xi-Ming [4 ]
Wang, Qing-Ping [3 ]
Li, Jun [1 ]
Zhang, Li [1 ]
机构
[1] Univ South China, Dept Gastroenterol, Affiliated Hosp 2, Hengyang 421001, Hunan, Peoples R China
[2] China Med Univ, Dept Gastroenterol, Shaoxing Hosp, Shaoxing 312030, Zhejiang, Peoples R China
[3] China Med Univ, Dept Clin Lab, Shaoxing Hosp, Shaoxing 312030, Zhejiang, Peoples R China
[4] Cent S Univ, Dept Clin Lab, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China
关键词
rosiglitazone; peroxisome proliferator-activated receptor gamma; gastric cancer; lymphangiogenesis; LYMPHATIC ENDOTHELIAL-CELLS; PPAR-GAMMA; BREAST-CANCER; NODE MICROMETASTASIS; FACTOR-C; VEGF-C; EXPRESSION; PROLIFERATION; DIFFERENTIATION; ADENOCARCINOMA;
D O I
10.3892/or.2013.2704
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Gastric cancer mainly metastasizes via lymphatic vessels. Thus, it is critical to identify efficacious chemopreventive agents for lymphangiogenesis. The present study was undertaken to explore the effects of rosiglitazone (ROSI) on the growth and lymphangiogenesis of human gastric cancer. We established a model of gastric cancer by subcutaneously inoculating the human gastric cancer cell line SGC-7901 into nude mice. Mice were randomly divided into 4 groups and each group received a different agent by oral gavage. The control group received normal saline and treatment groups received different doses of ROSI once every 2 days. The growth of the tumor in vivo was assessed by measuring tumor volume. After 42 days, the mice were sacrificed and the tumors were removed. H&E staining was used to observe the histomorphological features; immunohistochemistry staining for lymphatic vessel density (LVD) was used to evaluate tumor lymphangiogenesis, RT-PCR was performed to determine the mRNA expression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor-3 (VEGFR-3), and western blotting was used to detect the protein expression of VEGF-C and VEGFR-3. Compared with the control group, all treatment groups had smaller tumor volume and higher tumor growth inhibitory rate every day. The number of typical tumor cells in the control group was higher compared to that in the treatment groups, and the highest level of LVD was found in the control group. Furthermore, both the expression of VEGF-C and VEGFR-3 mRNA and proteins in the control group were significantly higher compared to those in the treatment groups. Markedly, these changes were correlated in a dose-dependent manner with ROSI. These results demonstrated that, through simultaneously blocking the expression of VEGF-C and VEGFR-3, ROSI suppresses lymphangiogenesis. This may represent a powerful therapeutic approach for controlling gastric cancer cell growth and metastasis.
引用
收藏
页码:2705 / 2712
页数:8
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