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脂肪细胞谷氨酰胺合成酶抑制结肠癌细胞的腹腔转移及血管生成
Glutamine synthetase from adipocytes inhibits peritoneal metastasis and angiogenesis of colon cancer in mice
- 第三军医大学学报 2018年40卷第1期 页码：70-75
- 作者机构：
400038 重庆, 第三军医大学西南医院肿瘤科
- 作者简介：
[ 缪洪明, E-mail:hongmingmiao@sina.com MIAO Hongming, E-mail:hongmingmiao@sina.com
[ 梁后杰, E-mail:lianghoujie@sina.com LIANG Houjie, E-mail:lianghoujie@sina.com
- 基金信息：国家自然科学基金青年科学基金(81702929)
DOI：10.16016/j.1000-5404.201706096
中图分类号： R345;R730-37;R735.35收稿：2017-06-19，
修回：2017-10-09，
纸质出版：2018-01-15
- 稿件说明：
移动端阅览
陈晓珍, 李一飞, 张璇, 等. 脂肪细胞谷氨酰胺合成酶抑制结肠癌细胞的腹腔转移及血管生成[J]. 第三军医大学学报, 2018,40(1):70-75.
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.
陈晓珍, 李一飞, 张璇, 等. 脂肪细胞谷氨酰胺合成酶抑制结肠癌细胞的腹腔转移及血管生成[J]. 第三军医大学学报, 2018,40(1):70-75. DOI： 10.16016/j.1000-5404.201706096.
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
2
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
2
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
GS
)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
GS
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
GS
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
2
Western blot检测结果显示
Tg
GS
小鼠较WT小鼠脂肪细胞GS蛋白水平显著上调(
P
<
0.05)。Tg
GS
小鼠较WT小鼠腹腔移植瘤数量明显减少[(6.33±4.04)
vs
(16.00±6.56)
P
<
0.05
]
体积明显减小[(2.35±1.93)
vs
(9.37±5.07)
P
<
0.01
]
。免疫组化结果显示
Tg
GS
小鼠肿瘤血管生成明显少于WT小鼠(
P
<
0.05)。体外小管形成实验显示Tg
GS
组较WT组HUVECs小管形成总长度明显缩短(
P
<
0.05);CCK8实验显示Tg
GS
组及WT组HUVECs的增殖差异无统计学意义(
P
>
0.05);Transwell实验显示Tg
GS
组HUVECs细胞迁移数量明显少于WT组[(15.33±5.50)
vs
(78.33±13.58)
P
<
0.01
]
。
结论
2
脂肪细胞GS可抑制结肠癌腹腔转移及肿瘤血管生成。
Abstract
Objective
2
To determine the effect of glutamine synthetase (GS) derived from adipocytes on intraperitoneal metastasis and angiogenesis of colon cancer.
Methods
2
Wide type(WT)and transgenetic mice (Tg
GS
) 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
6
cells in the WT mice and Tg
GS
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
GS
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
2
Western blotting showed that the expression level of GS protein in the adipocytes of Tg
GS
mice was significantly increased than that in WT mice (
P
<
0.05). In the xenograft model
there were notably less (6.33±4.04
vs
16.00±6.56
P
<
0.05) and smaller(2.35±1.93
vs
9.37±5.07
P
<
0.01) tumors in the Tg
GS
mice when compared with the WT mice. Immunohistochemical assay showed that the angiogenesis in Tg
GS
mice were obviously less than that in WT mice(
P
<
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
GS
mice than those with the medium from the WT mice group (
P
<
0.05). CCK8 assay displayed that there was no significant difference in the cell proliferation of HUVECs between the 2 kinds of media (
P
>
0.05).Transwell chamber test showed that there were less migrated cells in the HUVECs with Tg
GS
culture medium than those with WT culture medium (15.33±5.50
vs
78.33±13.58
P
<
0.01).
Conclusion
2
Adipocyte GS can inhibits peritoneal metastasis and tumor angiogenesis of colon cancer.
关键词
Keywords
references
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