摘要
目的:基于PI3K/AKT信号通路探讨达沙替尼(dasatinib,DAS)对乳腺癌MCF-7细胞生物学行为的影响。方法:分别使用噻唑蓝(methyl thiazolyl tetrazolium,MTT)法、Transwell法、流式细胞术和Western blotting法检测DAS不同浓度(0、2、6、10μmol/L)作用下MCF-7细胞增殖、侵袭和迁移、细胞凋亡以及PI3K/AKT信号通路相关蛋白表达情况。同时设置对照组(溶媒对照)、DAS组(DAS 10μmol/L)、PI3K抑制剂组(LY29400220μmol/L)、联合组(DAS 10μmol/L+LY29400220μmol/L),比较各组细胞增殖、侵袭和迁移、细胞凋亡以及PI3K/AKT信号通路相关蛋白表达情况。结果:随着DAS作用浓度的升高,MCF-7细胞增殖抑制率和细胞凋亡率升高(P<0.05),侵袭细胞数、迁移细胞数和PI3K、p-PI3K、p-AKT蛋白表达降低(P<0.05)。与对照组相比,DAS组、PI3K抑制剂组、联合组MCF-7细胞增殖抑制率和细胞凋亡率升高(P<0.05),PI3K、p-PI3K、p-AKT蛋白表达降低。与PI3K抑制剂组、DAS组相比,联合组MCF-7细胞增殖抑制率和细胞凋亡率升高,PI3K、p-PI3K、p-AKT蛋白表达降低(P<0.05)。结论:DAS能抑制乳腺癌MCF-7细胞增殖、侵袭和迁移能力,诱导细胞凋亡,其机制可能与调控PI3K/AKT信号通路有关。
Objective:To explore the effects of dasatinib(DAS)on biological behaviors of breast cancer MCF-7 cells based on PI3K/AKT signaling pathways.Methods:The proliferation,invasion,migration and apoptosis of MCF-7 cells,and expressions of PI3K/AKT signaling pathway related proteins after treatment with different concentrations of DAS(0,2,6,10μmol/L)were detected by methyl thiazolyl tetrazolium(MTT)assay,Transwell assay,flow cytometry and Western blotting,respectively.The control group(solvent control),DAS group(DAS 10μmol/L),PI3K inhibitor group(LY29400220μmol/L)and combination group(DAS 10μmol/L+LY29400220μmol/L)were set up.The cells proliferation,invasion,migration,apoptosis and expressions of PI3K/AKT signaling pathway related proteins were compared among different groups.Results:With the increase of DAS concentration,proliferation inhibition rate and apoptosis rate of MCF-7 cells were increased(P<0.05),while number of invasion and migration cells,and expressions of PI3K,p-PI3K and p-AKT were decreased(P<0.05).Compared with control group,proliferation inhibition rate and apoptosis rate of MCF-7 cells were increased(P<0.05),while expressions of PI3K,p-PI3K and p-AKT were decreased in the other three groups.Compared with PI3K inhibitor group and DAS group,proliferation inhibition rate and apoptosis rate of MCF-7 cells were increased,while expressions of PI3K,p-PI3K and p-AKT were decreased in combination group(P<0.05).Conclusion:DAS can inhibit proliferation,invasion and migration of breast cancer MCF-7 cells,and induce apoptosis.The mechanism may be related to the regulation of PI3K/AKT signaling pathways.
作者
沈云燕
邱琦
SHEN Yunyan;QIU Qi(Outpatient Office,the Second Affiliated Hospital of Soochow University,Jiangsu Suzhou 215004,China)
出处
《现代肿瘤医学》
CAS
2024年第7期1194-1199,共6页
Journal of Modern Oncology
基金
江苏省卫生健康委员会科研项目(编号:JJ2019M066)
江苏省临床医学科技专项(编号:BL2017044)。
