中国临床药理学与治疗学2024，Vol.29Issue(6)：645-652,8.DOI:10.12092/j.issn.1009-2501.2024.06.006
新型溴苯取代的三氟甲基苯并环戊酮WW02对肺癌细胞增殖的影响及其分子机制
Effects of a new bromobenzene substituted trifluoromethyl benzocy-clopentanone WW02 on the proliferation of lung cancer cells
摘要
Abstract
AIM:To investigate the molecular mechanism of a novel bromobenzene substituted trifluoromethylbenzo Cyclopentanone WW02 inhib-iting the viability and proliferation of human lung cancer A549 and H1299 cells.METHODS:The ef-fect of different concentrations of WW02(6.25,12.5,25,50 μg/mL)on cell viability and prolifera-tion of A549 and H1299 were measured using CCK-8 and EdU methods.After 24 hours of stimulation of A549 and H1299 cells with different concentra-tions of WW02,the changes in Akt and mTOR phos-phorylation levels under different concentrations of WW02 were detected through Western blot as-say.Macromolecular docking was carried out be-tween WW02,AKT and mTOR through MOE Dock.RESULTS:After treating A549 and H1299 cells with WW02 using different concentrations(6.25,12.5,25,50 μg/mL),the activity of A549 and H1299 cells decreased in a concentration dependent manner compared with the DMSO control group(P<0.05).The proliferation of cells showed a concentration dependent decrease compared to the DMSO con-trol group(P<0.05).Compared with the DMSO con-trol group,after 24 hours of WW02 stimulation,the phosphorylation levels of Akt and mTOR in A549 cells decreased under the concentration of WW02(12.5,25,50 μg/mL,P<0.05).Compared with the DMSO control group,the phosphorylation levels of Akt and mTOR in H1299 cells decreased af-ter 24 hours of WW02 stimulation(25,50 μg/mL,P<0.05).Based on pattern analysis,it was found that WW02 had a strong binding with Akt and mTOR,with the highest score of-8.3 kcal/mol for WW02 and mTOR,while the highest score for WW02 and Akt was-7.3 kcal/mol.CONCLUSION:WW02 inhib-its the activity and proliferation of lung cancer A549 and H1299 cells,and its mechanism of action may be achieved by directly binding to Akt and mTOR proteins to inhibit Akt and mTOR phosphory-lation.关键词
溴苯取代的三氟甲基苯并环戊酮/细胞增殖/Akt/mTOR/WW02Key words
bromobenzene substituted trifluoro-methyl benzocyclopentanone/cell proliferation/Akt/mTOR/WW02分类
医药卫生引用本文复制引用
李玉磊,李萍,马金珠,凌云云,左梦雨,丁振宇,薛良军..新型溴苯取代的三氟甲基苯并环戊酮WW02对肺癌细胞增殖的影响及其分子机制[J].中国临床药理学与治疗学,2024,29(6):645-652,8.基金项目
安徽省高校科研编制重大项目(2022AH040179) （2022AH040179）
皖南医学院校级自然科学研究重点项目(WK2020Z16) （WK2020Z16）
皖南医学院大学生科研项目(WK2022XS08) （WK2022XS08）
国家级大学生创新创业计划项目(202210368058) （202210368058）
