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

Radiosensitizaton of insulin like growth factor-1 receptor inhibitor AG1024 on growth of esophageal cancer cells

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.