胰岛素样生长因子1受体抑制剂对甲磺酸伊马替尼继发耐药性胃肠道间质瘤细胞增殖及蛋白激酶B蛋白磷酸化的影响  

Effect of insulin-like growth factor 1 receptor inhibitor on proliferation and phosphorylated protein kinase B of secondary imatinib mesylate-resistant gastrointestinal stromal tumor cells

作　　者：秦龙[1] 罗彬予 李婷[1] 吕真冰 QIN Long;LUO Bin-yu;LI Ting;LYU Zhen-bing(Department of Gastrointestinal and Hernia Surgery,Nanchong Central Hospital,the Second Clinical School of North Sichuan Medical College,Nanchong 637000,China)

机构地区：[1]川北医学院第二临床学院/南充市中心医院胃肠疝外科,四川省南充市637000

出　　处：《广西医学》2021年第6期703-706,724,共5页Guangxi Medical Journal

基　　金：国家自然科学基金(81401927);四川省南充市科技计划(18YFZJ0015)。

摘　　要：目的探讨胰岛素样生长因子1受体(IGF-1R)抑制剂AG-1024对甲磺酸伊马替尼继发耐药性胃肠道间质瘤(GIST)细胞增殖及蛋白激酶B(Akt)蛋白磷酸化的影响。方法采用甲磺酸伊马替尼诱导GIST-T1细胞以建立继发耐药性细胞系。将继发耐药性GIST-T1细胞分为对照组(0μmol/L AG-1024)以及5μmol/L、10μmol/L、20μmol/L AG-1024组,给予相应浓度AG-1024干预12 h、24 h、48 h后,检测细胞增殖情况。将继发耐药性GIST-T1细胞分为AG-102412 h组、AG-102424 h组、AG-102448 h组和对照组,各AG-1024组加入10μmol/L AG-1024干预相应的时间,对照组加入等体积的二甲亚砜(干预即刻收集细胞),检测各组细胞Akt蛋白、磷酸化Akt蛋白表达水平。结果(1)各浓度AG-1024组的吸光度值呈下降趋势;同一时间点,各浓度AG-1024组的吸光度值均低于对照组,且10μmol/L AG-1024组与20μmol/L AG-1024组的吸光度值低于5μmol/L AG-1024组(均P<0.05),但10μmol/L AG-1024组与20μmol/L AG-1024组差异无统计学意义(P>0.05)。(2)AG-102412 h组、AG-102424 h组、AG-102448 h组和对照组Akt蛋白表达水平差异无统计学意义(P>0.05);对照组、AG-102412 h组、AG-102424 h组、AG-102448 h组细胞磷酸化Akt蛋白表达水平依次降低(均P<0.05)。结论IGF-1R抑制剂AG-1024可抑制甲磺酸伊马替尼继发耐药性GIST-T1细胞的增殖,且呈一定的时间依赖性,抑制磷脂酰肌醇3-激酶/Akt信号通路中Akt的磷酸化可能是其作用机制之一。Objective To investigate the effect of insulin-like growth factor 1 receptor(IGF-1R)inhibitor AG-1024 on the proliferation and phosphorylated protein kinase B(Akt)of secondary imatinib mesylate-resistant gastrointe stinal stromal tumor(GIST)cells.Methods GIST-T1 cells were induced by imatinib mesylate to develop secondary drug resistant cell line.GIST-T1 cells with secondary drug resistance were divided into control group(0μmol/L AG-1024),5μmol/L,10μmol/L,and 20μmol/L AG-1024 groups,treated with corresponding concentrations of AG-1024 for 12,24 and 48 hours,and then the proliferation of the cells was detected.GIST-T1 cells with secondary drug resistance were divided into 12 h AG-1024 group,24 h AG-1024 group,48 h AG-1024 group and control group,the AG-1024 groups were treated with 10μmol/L AG-1024 for corresponding time,the control group was added with equivalent volume of dimethyl sulfoxide(the cells were collected at the right moment of intervention initiation),the expression levels of Akt and phosphorylated Akt proteins of the cells were detected in each group.Results(1)A value was declined in each AG-1024 group;at the same time point,the AG-1024 groups exhibited a lower A value than the control group,and the 10μmol/L and 20μmol/L AG-1024 groups had a lower A value than the 5μmol/L AG-1024 group(all P<0.05),whereas there was no statistically significant difference between the 10μmol/L AG-1024 group and the 20μmol/L AG-1024 group(P>0.05).(2)The expression level of Akt protein in the 12 h,24 h or 48 h AG-1024 group did not statistically differ from the level in the control group(P>0.05);the expression level of phosphorylated Akt protein decreased in the sequence of the control group,the 12 h AG-1024 group,the 24 h AG-1024 group and the 48 h AG-1024 group(all P<0.05).Conclusion IGF-1R inhibitor AG-1024 could inhibit the proliferation of secondary imatinib mesylate-resistant GIST-T1 cells in a time-dependent manner,and one of its action mechanisms is likely to be the inhibition of phosphorylated Akt in p

关 键 词：胃肠道间质瘤 继发性耐药 甲磺酸伊马替尼 胰岛素样生长因子1受体抑制剂 蛋白激酶B 磷酸化 体外实验 

分 类 号：R735[医药卫生—肿瘤]