抑制磷脂酰肌醇-3-羟基激酶/蛋白激酶B信号传导通路对宫颈癌放疗增敏的作用  

Inhibition of PI3K/AKT pathway enhances radiosensitization of cervical cancer in vivo

作　　者：刘艺[1] 崔保霞[1] 乔云波[1] 李贞[2] 张友忠[1] 马道新[3] 姜洁[1] 孔北华[1] 

机构地区：[1]山东大学齐鲁医院妇产科,济南250012 [2]山东大学齐鲁医院肿瘤中心放疗科,济南250012 [3]山东大学齐鲁医院肿瘤中心实验室,济南250012

出　　处：《现代妇产科进展》2010年第4期278-281,共4页Progress in Obstetrics and Gynecology

基　　金：山东省中青年科学家奖励基金(No:2006BS03060);国家自然科学基金(No:30400475)资助

摘　　要：目的:探讨抑制磷脂酰肌醇-3-羟基激酶/蛋白激酶B(PI3K/AKT)信号传导通路对宫颈癌的放疗增敏作用。方法:选用LY294002为PI3K阻滞剂。培养PI3K功能活性和AKT磷酸化水平稳定的人宫颈癌HeLa细胞株,皮下注射于BALB/C裸鼠体内,建立裸鼠宫颈癌移植瘤模型。随机将荷瘤裸鼠分为空白对照组、单纯放疗组、单纯药物组(LY294002)和联合治疗组(放疗+LY294002)。应用Western blotting检测各组AKT磷酸化(phospho-Ser473AKT)水平。通过克隆形成实验检测LY294002在体内的放射增敏作用。长期观察肿瘤体积的变化并绘制肿瘤生长曲线。结果:Western blotting显示,联合治疗组的AKT去磷酸化现象最显著。克隆形成实验显示,LY294002与放射治疗对肿瘤细胞生长的抑制在各剂量水平均表现出协同作用(P<0.05)。肿瘤生长曲线表明联合治疗组的肿瘤体积增长最缓慢。结论:PI3K阻滞剂显著增强宫颈癌对放射治疗的敏感性。Objective：To investigate whether inhibition of PI3K/AKT pathway enhances radiosensitization of cervical cancer in vivo.Methods：HeLa cells with sustained PI3K activity and AKT phosphorylation were injected subcutaneously into BALB/C nude mice to establish tumors.LY294002 was selected as PI3K inhibitor.The tumor bearing mice were randomly assigned to control,LY294002 alone,radiation alone or combined application of LY294002 and radiation groups.AKT phosphorylation（phospho-Ser 473 AKT）was evaluated by Western blotting.The survival efficiency of tumor cells after treatments was measured by clonogenic assays.The long-term tumor volume was observed for tumor growth delay curve.Results：Most conspicuous reduction of AKT phosphorylation was observed in the combined application group.Clonogenic assay showed that the synergism of radiation and LY294002 in the suppression of cervical cancer cell survival was tested at each radiation dose（P0.05）.Tumor growth delay curve showed the lowest increase of tumor volume in combined application group.Conclusion：PI3K inhibition enhances radiosensitization of human cervical cancer significantly in vivo.

关 键 词：宫颈肿瘤 辐射增敏药 PI3K抑制剂 LY294002 动物模型 

分 类 号：R737.33[医药卫生—肿瘤]