丙泊酚抑制STAT3磷酸化对乳腺癌MCF-7细胞转移的影响  

Effect of propofol on metastasis of breast cancer MCF-7 cells by inhibiting phosphorylation of STAT3

作　　者：田诗意 吴悠 李远[2] 彭明清[1] TIAN Shiyi;WU You;LI Yuan;PENG Mingqing(Department of Anesthesiology,Yongchuan Hospital Affiliated of Chongqing Medical University,Chongqing 402160,China;Central Laboratory,Yongchuan Hospital Affiliated of Chongqing Medical University,Chongqing 402160,China)

机构地区：[1]重庆医科大学附属永川医院麻醉科,重庆402160 [2]重庆医科大学附属永川医院中心实验室,重庆402160

出　　处：《肿瘤》2020年第8期549-556,共8页Tumor

基　　金：重庆医科大学附属永川医院研究生创新基金(编号:YJSCX201902)。

摘　　要：目的:探讨丙泊酚对体外培养的人乳腺癌MCF-7细胞迁移、侵袭和新生血管形成能力的影响,以及其可能的分子作用机制。方法:CCK-8法检测不同质量浓度的丙泊酚对乳腺癌MCF-7细胞增殖能力的影响。将MCF-7细胞随机分为对照组和25μg/mL丙泊酚处理组,采用蛋白质印迹法检测E-钙黏蛋白(E-cadherin)、信号转导和转录激活因子3(signal transducers and activators of transcription 3,STAT3)以及磷酸化STAT3蛋白的表达水平。采用Transwell小室迁移和侵袭实验以及体外血管拟态形成实验分别检测细胞迁移、侵袭和新生血管生成能力的变化。应用AutoDock软件对丙泊酚和STAT3蛋白进行分子对接模拟分析。结果:丙泊酚可抑制乳腺癌MCF-7细胞增殖(P<0.001)。与对照组相比,25μg/mL丙泊酚处理组中E-cadherin蛋白表达水平升高(P<0.05),磷酸化STAT3蛋白表达水平降低(P<0.05),而STAT3蛋白表达无明显差异(P>0.05)。相较于对照组,丙泊酚可显著抑制MCF-7细胞的迁移、侵袭以及新生血管的形成(P<0.0001、P<0.0001和P<0.05)。丙泊酚的氢原子能够与STAT3蛋白精氨酸(arginine,ARG)-688残基的氧原子形成氢键,从而增强其靶向作用。结论:丙泊酚可通过靶向作用STAT3抑制STAT3磷酸化,使乳腺癌MCF-7细胞增殖、迁移、侵袭和新生血管形成的能力降低,从而发挥抗肿瘤作用。Objective:To investigate the effects of propofol on the migration,invasion and angiogenesis of human breast cancer MCF-7 cells in vitro,and the related molecular mechanism.Methods:The viability of MCF-7 cells treated with different concentrations of propofol was estimated by CCK-8.Then MCF-7 cells were divided into two groups randomly:control group,propofol group(25μg/mL).The expressions of E-cadherin,signal transducers and activators of transcription 3(STAT3)and phosphorylated STAT3 proteins in MCF-7 cells were detected by Western blotting.The changes of migration,invasion and angiogenesis of MCF-7 cells were recorded by Transwell chamber assay and vascular mimicry assay,respectively.The molecular docking of propofol and STAT3 protein was simulated by AutoDock software.Results:The cell viability of MCF-7 cells was inhibited by propofol(P<0.001).Compared with the control group,the expression of E-cadherin was increased in propofol group(P<0.05)and the expression of phosphorylated STAT3 protein was decreased(P<0.05).There was no significantly difference between the two groups in the expression of STAT3 protein(P>0.05).The migration,invasion and angiogenesis abilities were significantly inhibited in propofol group(P<0.0001,P<0.0001,P<0.05).The hydrogen bond was formed between propofol and arginine(ARG)-688 residue of STAT3 protein for improving the targeting ability.Conclusion:Propofol can inhibit migration,invasion and angiogenesis abilities of breast cancer MCF-7 cells by targeting STAT3 directly to inhibit phosphorylation of STAT3,which confirms that propofol has anti-breast cancer effects.

关 键 词：乳腺肿瘤 二异丙酚 STAT3转录因子 分子对接模拟 

分 类 号：R737.9[医药卫生—肿瘤]