脂肪细胞谷氨酰胺合成酶抑制结肠癌细胞的肝、肺转移

目的 探讨脂肪细胞谷氨酰胺合成酶(glutamine synthetase,GS)对结肠癌细胞迁移及转移的调控作用.方法 分别用野生型(WT)小鼠和脂肪细胞GS转基因(TgGS)小鼠的脂肪细胞条件培养基处理结肠癌MC38及CT26细胞,采用CCK-8法检测细胞增殖活力,流式细胞仪检测细胞凋亡,划痕实验和Transwell实验检测细胞迁移能力;通过尾静脉注射结肠癌MC38细胞建立肿瘤血行转移小鼠模型,病理切片观察肝、肺组织的转移情况.结果 CCK-8检测发现脂肪细胞条件培养基对结肠癌MC38及CT26细胞的增殖无明显影响(P＞0.05);流式细胞仪检测发现脂肪细胞条件培养基对结肠癌MC38及CT26细胞的凋亡无明显影响(P＞0.05);划痕实验和Transwell实验结果显示TgGS小鼠脂肪细胞条件培养基可以抑制结肠癌MC38及CT26细胞的迁移能力(P＜0.05);尾静脉注射结肠癌MC38细胞后,与WT小鼠比较,TgGS小鼠肺转移瘤的大小及数量明显减少(P＜0.01),且TgGS小鼠较WT小鼠更不易发生肝转移(P＜0.0l).结论 脂肪细胞GS可以抑制结肠癌细胞的迁移及转移.

Glutamine synthetase from adipocytes inhibits hepatic and pulmonary metastasis of colon cancer cells

Objective To investigate the modulation effect of glutamine synthetase (GS) from adipocytes on migration and metastasis of colon cancer cells.Methods The MC38 and CT26 colon cancer cells were treated with adipocyte conditional media from wild-type mice and transgenetic mice (TgGS) respectively.CCK-8 assay was used to detect the proliferation of the treated MC38 and CT26 cells.Flow cytometry was adopted to measure the apoptosis of the treated MC38 and CT26 cells.Cell scratch assay and Transwell chamber test was employed to detect the migration of the treated MC38 and CT26 cells.Then the MC38 xenograft model was established by tail vein injection in wild-type mice and TgGS transgenetic mice respectively,HE staining was used to observe the migration and invasion of xenograft.Results CCK-8 assay found that the 2 kinds of adipocyte conditional media barely influenced the proliferation of the MC38 and CT26 cells (P ＞ 0.05).The results of flow cytometry showed that the 2 kinds of adipocyte conditional media had no effect on the apoptosis of 2 kinds of cells (P ＞ 0.05).Cell scratch assay and Transwell chamber test illustrated that GS conditional media inhibited the migration of the MC38 and CT26 cells (P ＜ 0.05).In vivo test,there were less and smaller pulmonary xenografts in the transgenetic mice than the wild-type mice after tail vein injection of MC38 cells (P ＜0.01).And liver metastases were more common in the wild-type mice than the transgenetic mice (P ＜ 0.01).Conclusion GS from adipocytes can inhibit migration and metastasis of colon cancer cells.