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胰岛素样生长因子-1受体抑制剂对食管癌放疗增敏的研究 被引量:2

Radiosensitizaton of insulin like growth factor-1 receptor inhibitor AG1024 on growth of esophageal cancer cells
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摘要 目的 探讨胰岛素样生长因子-1受体(IGF-1 R)抑制剂AG1024对人食管癌EC9706细胞的放疗增敏作用及机制.方法 将AG1024(10 μmol/L)加入人食管癌细胞EC9706后48 h,与单放组细胞同时置于6MV-X射线下照射0、1、2、4、6、8Gy,细胞克隆法绘制生长曲线;流式细胞仪检测各组肿瘤细胞周期改变,Western blot法检测IGF-1R下游蛋白表达.结果 加入AG1024后,食管癌细胞放射敏感性增加,流式细胞仪检测联合组凋亡细胞明显增多,较单放组差异有统计学意义[(27.3±6.1)%比(13.4±4.8)%,P<0.05].Western blot法检测磷酸化蛋白激酶B(p-Akt)及磷酸化细胞外信号调节激酶1/2(p-ERK1/2)表达下降.结论 IGF-1R抑制剂AG1024能增加食管癌细胞株EC9706的放射敏感性,而促进细胞凋亡,下调磷酸肌醇3激酶(PI3K)/Akt和丝裂原活化蛋白激酶(MAPK)信号传导路径可能是其机制之一. Objective To investigate the effect of insulin like growth factor-1 receptor (IGF-1 R) inhibitor AG1024 on the radiosensitivity of esophageal cancer EC9706 cells and the underlying mechanisms.Methods Esophageal cancer EC9706 cells were treated by AG1024 (10 μmol/L) for 48 hours,and then the treated cells were received 0,1,2,4,6,8 Gy 6MV X-ray in total respectively.After radiation,we made the cell growth curve,tested the cell cycle by flow cytometry and the IGF-1R downstream protein by western blotting.Results The EC9706 cell were more radiosensitive after AG1024 treatment,and the apoptosis cells significantly increased compared with untreated cells.The expression of phosphorylated protein kinase B (p-Akt) and phosphorylated extracellular signal-regulated kinase (p-ERK1/2) protein decreased after treatment [(27.3 ±6.1)% vs.(13.4 ±4.8)%,P 〈0.05].Conclusion IGF-1R inhibitor AG1024 could enhance the radiosensitivity on the growth of esophageal cancer cell line EC9706,and induce cell apoptosis and down-regulation of phosphatidylinositol 3 kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) pathways might be the underlying cause of the change.
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2015年第3期550-552,共3页 Chinese Journal of Experimental Surgery
基金 河南省科技厅科技基础与前沿技术研究计划项目(1123004-10296)
关键词 食管癌 胰岛素样生长因子-1受体 放疗增敏 Esophageal cancer Insulin-like growth factor-1 receptor Radiosensitivity
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