摘要
目的明确硼替佐米(bortezomib,PS341)和PLK1抑制剂处理肿瘤细胞HeLa、A549后细胞增殖的变化,探索不同药物组合使用的抗肿瘤作用机制。方法CCK-8法检测不同浓度分组的药物处理A549、HeLa细胞后的生长曲线;采用PI染色法检测PLK1抑制剂BI2536、GW843682X与蛋白酶体抑制剂PS341的合并使用对肿瘤细胞周期的影响;采用Western blot检测细胞周期相关蛋白和PLK1的蛋白表达水平。结果PLK1抑制剂BI2536、GW843682X均明显抑制A549、HeLa细胞生长并使其阻滞在G_(2)/M期,加入蛋白酶体抑制剂PS341后细胞增殖抑制被削弱、G_(2)/M期阻滞的细胞减少、周期蛋白cyclin E1异常积累。结论PS341可明显减弱PLK1抑制剂的细胞增殖抑制效果,认为PLK1抑制剂与PS341联合使用需考虑药效减弱的风险,推测相关分子机制涉及细胞周期蛋白代谢异常。
Aim To investigate the changes of cell proliferation in A549 and HeLa tumor cells treated with bortezomib and PLK1 inhibitors,and to explore the anti-tumor mechanism of different drug combinations.Methods The growth curves of A549 and HeLa cells treated with different concentration groups were detected by CCK-8.The combined use of PLK1 inhibitors BI2536,GW843682X and proteasome inhibitor PS341 on tumor cell cycle was detected by PI staining.The expression levels of cyclins and PLK1 were detected by Western blot.Results PLK1 inhibitors BI2536 and GW843682X significantly inhibited the growth of A549 and HeLa cells and blocked them in G_(2)/M phase.The addition of proteasome inhibitor bortezomib(PS341)weakened the cell proliferation inhibition,decreased the number of cells blocked in G_(2)/M phase and abnormal accumulation of cyclin E1.Conclusions Bortezomib can significantly reduce the inhibitory effect of PLK1 inhibitors on cell proliferation,and the combined use of bortezomib and PLK1 inhibitors should be considered to have the risk of drug efficacy reduction,and it is speculated that the related molecular mechanism may involve the abnormal metabolism of cyclin.
作者
胡玲
王英
蒋斌元
胡锦跃
HU Ling;WANG Ying;JIANG Bin-yuan;HU Jin-yue(Yongchuan Hospital of Chongqing Medical University,Chongqing 402160,China;The First Affiliated Hospital of Jiamusi University,Jiamusi,Heilongjiang 154000,China;Changsha Central Hospital Affiliated to University of South China,Changsha 410004,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2023年第11期2115-2121,共7页
Chinese Pharmacological Bulletin
基金
湖南省自然科学基金面上项目(No 2020JJ4636)
湖南省研究生科研创新项目(No CX20200983)。
