蛋白激酶全抑制分析揭示KG-1细胞增殖的分子机制  

Comprehensive protein kinase inhibition analysis reveals the molecu-lar mechanism of KG-1 proliferation

作　　者：段毓 徐凝馨 曹琼 杨恺 王金娟 刘思瑾 贾峰峰 刘建兵[1] 李莉[1] DUAN Yu;XU Ningxin;CAO Qiong;YANG Kai;WANG Jinjuan;LIU Sijin;JIA Fengfeng;LIU Jianbing;LI Li(Department of Cell Biology and Genetics,School of Basic Medicine,Shanxi Medical University,Taiyuan 030001,Shanxi,China;Department of Medical Genetics and Prenatal Diagnosis,Maternal and Child Health Hospital of Jiaozuo City,Jiaozuo 454100,Henan,China;Department of Dermatology,The First Hospital of Peking University Taiyuan Hospital,Taiyuan Central Hospital,Taiyuan 030009,Shanxi,China;Taiyuan Technology Transfer Promotion Center,Taiyuan 030006,Shanxi,China)

机构地区：[1]山西医科大学基础医学院医学细胞生物与遗传学教研室,山西太原030001 [2]焦作市儿童医院,河南焦作454100 [3]太原市中心医院,山西太原030009 [4]太原技术转移促进中心,山西太原030006

出　　处：《中国临床药理学与治疗学》2024年第6期621-628,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：山西省留学归国留学生科研资助计划(2020-076);山西省自然科学基金(自由探索类)(20210302123307);国家自然科学基金面上项目(82272622)。

摘　　要：目的:通过分析KG-1细胞对各种蛋白激酶抑制剂的反应,探讨其增殖的分子机制。方法:采用CCK-8法、实时荧光定量PCR(qRT-PCR)和Western-blot检测各种蛋白激酶抑制剂对KG-1细胞增殖、相关基因mRNA表达水平以及FGFR1下游信号通路蛋白磷酸化水平的影响。结果:NVP-BGJ398和PD173074有效抑制KG-1细胞的增殖,表明FGFR及其下游信号通路在KG-1细胞增殖过程中具有关键作用。使用FGFR抑制剂处理后,p-FGFR1和p-STAT5水平显著下降(P<0.001),p-Akt水平稍有下降(P<0.05),并未影响p-ERK水平(P>0.05)。结论:FGFR1OP2-FGFR1主要作用于下游STAT5信号通路,以促进细胞增殖。蛋白激酶全抑制分析是一种可靠而直接的方法,可用于确定癌细胞增殖的分子机制。AIM:To investigate the molecular mechanisms of KG-1 cell proliferation by profiling its responses to various protein kinase inhibitors.METHODS:CCK-8 assay,real time quantitative PCR(qRT-PCR)and Western-blot were used to detect the effect of various protein kinase inhibitors on KG-1 cell proliferation,the expression levels of mRNA and phosphorylation level of signaling pro-teins in the FGFR1 downstream pathways.RE-SULTS:NVP-BGJ398 and PD173074 effectively in-hibited the proliferation of KG-1 cells,indicative of a crucial role of FGFR downstream signaling.After treatment with FGFR inhibitors,the levels of p-FG-FR1OP2-FGFR1 and p-STAT5 decreased significantly(P<0.001),p-AKT decreased slightly(P<0.05),with-out affecting the p-ERK level(P>0.05).CONCLU-SION:FGFR1OP2-FGFR1 mainly acts on the down-stream STAT5 signaling pathway to promote cell proliferation.Comprehensive protein kinase inhibi-tion analysis is a reliable and direct approach to identify functional drivers of cancer cell prolifera-tion.

关 键 词：KG-1细胞 蛋白激酶抑制剂 FGFR1OP2-FGFR1融合基因 STAT5 

分 类 号：R965.2[医药卫生—药理学]