南方医科大学学报2018，Vol.38Issue(4)：395-401,7.DOI:10.3969/j.issn.1673-4254.2018.04.05
促红细胞生成素通过激活Akt通路促进胶质瘤的快速增殖
Erythropoietin accelerates the proliferation of glioma cells via activating Akt pathway
摘要
Abstract
Objective To determine whether erythropoietin(EPO)promotes rapid proliferation of glioma through Akt pathway. Methods We detected the expression of EPO in human glioma tissues using immunohistochemistry. A nude mouse model bearing human glioma U87 cell xenograft was established and given intraperitoneal injection of EPO or saline every other day, and the tumor growth was observed.In the in vitro experiment,U87 cells were treated with PBS(control),EPO,or EPO with Akt inhibitor,and the expression of p-Akt and cyclin D1 was detected using Western blotting;the cell proliferation rate was determined using cell counting kit-8 and clone formation assay,and the cell cycle changes were analyzed with flow cytometry. Results Compared with low-grade glioma tissues, high-grade glioma tissues exhibited a significantly increased EPO expression(P=0.0002).In the tumor-bearing mice,EPO treatment significantly increased the expression of EPO(P=0.0006)and p-Akt (P=0.0003) in the tumor and obviously increased the tumor volume (P<0.0001) and weight (P=0.0003). In U87 cells cultured in vitro,EPO treatment obviously accelerated the cell proliferation(P=0.020 on day 3 and 0.028 on day 5),promoted clone formation(P=0.0010),and increased proliferation index(P=0.0028);EPO significantly enhanced the protein expression of p-Akt (P=0.0020) and cyclin D1 (P=0.0022). The application of Akt inhibitor significantly suppressed the effect of EPO in enhancing cyclin D1 and p-Akt expression(both P<0.0001)and promoting cell proliferation.Conclusion EPO can significantly accelerate the proliferation of glioma through Akt pathway.关键词
Akt信号通路/促红细胞生成素/胶质瘤/移植瘤/细胞增殖Key words
Akt signaling pathway/erythropoietin/glioma/xenograft/cell proliferation引用本文复制引用
刘自力,唐兆华,霍钢,陈飞兰,王文涛,曾纹鑫,陈鸿,李欣,陈宸..促红细胞生成素通过激活Akt通路促进胶质瘤的快速增殖[J].南方医科大学学报,2018,38(4):395-401,7.基金项目
国家自然科学基金(81306409) （81306409）
国家临床重点专科建设[财社{2011}170号] （）
重庆市教委科学技术研究(KJ1500219) （KJ1500219）
重庆市渝中区科技计划(20150108)Supported by National Natural Science Foundation of China(81306409). （20150108）
