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
段毓 1徐凝馨 2曹琼 3杨恺 1王金娟 1刘思瑾 1贾峰峰 4刘建兵 1李莉1
作者信息
- 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,太原 030001,山西
- 2. 焦作市儿童医院,焦作 454100,河南
- 3. 太原市中心医院,太原 030009,山西
- 4. 太原技术转移促进中心,太原 030006,山西
- 折叠
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.
Abstract
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/STAT5Key words
KG-1 cell line/protein kinase inhibi-tors/FGFR1OP2-FGFR1fusion gene/STAT5引用本文复制引用
基金项目
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)
出版年
2024
国家科技期刊平台
NSTL
万方数据