Glutamine synthetase from adipocytes inhibits peritoneal metastasis and angiogenesis of colon cancer in mice

Xiaozhen CHEN; Yifei LI; Xuan ZHANG; Hongming MIAO; Houjie LIANG

doi:10.16016/j.1000-5404.201706096

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Glutamine synthetase from adipocytes inhibits peritoneal metastasis and angiogenesis of colon cancer in mice

更新时间：2026-01-09

- Glutamine synthetase from adipocytes inhibits peritoneal metastasis and angiogenesis of colon cancer in mice
- Journal of Third Military Medical University Vol. 40, Issue 1, Pages: 70-75(2018)
- 作者机构：
  
  400038 重庆, 第三军医大学西南医院肿瘤科
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation for Young Scholars of China(81702929)
- DOI：10.16016/j.1000-5404.201706096
  CLC： R345;R730-37;R735.35
- Received：19 June 2017，
  
  Revised：2017-10-09，
  
  Published：15 January 2018
- 稿件说明：
移动端阅览
Xiaozhen CHEN, Yifei LI, Xuan ZHANG, et al. Glutamine synthetase from adipocytes inhibits peritoneal metastasis and angiogenesis of colon cancer in mice[J]. Journal of Third Military Medical University, 2018, 40(1): 70-75.
DOI：

Xiaozhen CHEN, Yifei LI, Xuan ZHANG, et al. Glutamine synthetase from adipocytes inhibits peritoneal metastasis and angiogenesis of colon cancer in mice[J]. Journal of Third Military Medical University, 2018, 40(1): 70-75. DOI： 10.16016/j.1000-5404.201706096.

摘要

目的

探讨脂肪细胞谷氨酰胺合成酶(glutamine synthetase

GS)对结肠癌腹腔转移及血管生成的影响。

方法

转基因小鼠的鉴定:Western blot检测野生型(WT)小鼠及脂肪细胞GS转基因(Tg

)小鼠脂肪细胞GS蛋白的表达。体内实验:分别构建WT小鼠及Tg

小鼠的腹腔转移模型

观察结肠癌细胞在腹腔的种植情况; 免疫组化检测移植瘤的血管生成情况。体外实验:取WT及Tg

小鼠的脂肪进行无菌培养

收集条件培养基; 通过小管形成实验、CCK8实验、Transwell实验观察条件培养基对人脐静脉内皮细胞(human umbilical vein endothelial cells

HUVECs)的小管形成、增殖及迁移的影响。

结果

Western blot检测结果显示

小鼠较WT小鼠脂肪细胞GS蛋白水平显著上调(

0.05)。Tg

小鼠较WT小鼠腹腔移植瘤数量明显减少[(6.33±4.04)

(16.00±6.56)

0.05

]

体积明显减小[(2.35±1.93)

(9.37±5.07)

0.01

]

。免疫组化结果显示

小鼠肿瘤血管生成明显少于WT小鼠(

0.05)。体外小管形成实验显示Tg

组较WT组HUVECs小管形成总长度明显缩短(

0.05);CCK8实验显示Tg

组及WT组HUVECs的增殖差异无统计学意义(

0.05);Transwell实验显示Tg

组HUVECs细胞迁移数量明显少于WT组[(15.33±5.50)

(78.33±13.58)

0.01

]

。

结论

脂肪细胞GS可抑制结肠癌腹腔转移及肿瘤血管生成。

Abstract

Objective

To determine the effect of glutamine synthetase (GS) derived from adipocytes on intraperitoneal metastasis and angiogenesis of colon cancer.

Methods

Wide type(WT)and transgenetic mice (Tg

) were firstly identified with Western blotting for the expression level of GS protein in the adipocytes.Then mouse model of peritoneal metastasis of colon cancer MC38 cells was established by intraperitoneally injecting 2.0×10

cells in the WT mice and Tg

mice. Then the cell implantation and tumor formation were observed.Immunohistochemical assay was used to detect the angiogenesis of the tumor mass.The fat tissues were harvested from WT and Tg

mice

and then the adipocytes were isolated and cultured to obtain the 2 kinds of adipocyte conditional media.Then tube formation assay

CCK8 assay

and Transwell chamber test were used to determine the effects of the 2 kinds of conditioned media on the tube formation

proliferation and migration in human umbilical vein endothelial cells (HUVECs).

Results

Western blotting showed that the expression level of GS protein in the adipocytes of Tg

mice was significantly increased than that in WT mice (

0.05). In the xenograft model

there were notably less (6.33±4.04

16.00±6.56

0.05) and smaller(2.35±1.93

9.37±5.07

0.01) tumors in the Tg

mice when compared with the WT mice. Immunohistochemical assay showed that the angiogenesis in Tg

mice were obviously less than that in WT mice(

0.05).The tube formation assay indicated that the total lengt

hs of tubules was significantly shorter in the HUVECs co-cultured with adipocyte conditional medium from the Tg

mice than those with the medium from the WT mice group (

0.05). CCK8 assay displayed that there was no significant difference in the cell proliferation of HUVECs between the 2 kinds of media (

0.05).Transwell chamber test showed that there were less migrated cells in the HUVECs with Tg

culture medium than those with WT culture medium (15.33±5.50

78.33±13.58

0.01).

Conclusion

Adipocyte GS can inhibits peritoneal metastasis and tumor angiogenesis of colon cancer.

关键词

Keywords

references

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