摘要
目的:探讨白杨素协同维奈托克诱导的急性髓系白血病(acute myeloid leukemia,AML)细胞凋亡的作用及其分子机制。方法:体外培养AML细胞系MV411和MOLM13,单独使用白杨素或联合维奈托克处理,CCK8法检测细胞活力;流式细胞术检测细胞的细胞周期和凋亡率;Western blot检测凋亡相关蛋白及蛋白激酶B(protein kinase B,PKB/Akt)/核因子κB(nuclear factor-κB,NF-κB)信号通路相关蛋白的表达变化。结果:CCK8法检测结果及流式细胞术检测显示,16和32μmol/L白杨素可显著抑制AML细胞活力,G1期细胞比例和凋亡比例显著增加。与白杨素或维奈托克单用组相比,联合用药组细胞的增殖能力显著降低,凋亡率显著增加。Western blot检测结果显示,随着白杨素浓度的增加,DNA修复酶多腺苷二磷酸核糖聚合酶[poly(ADP-ribose)polymerase,PARP]裂解体水平升高,Akt/NF-κB信号通路相关蛋白表达水平下调。与白杨素及维奈托克单用组相比,联合用药可显著上调PARP裂解体,下调Akt/NF-κB信号通路相关蛋白表达水平。结论:白杨素可通过细胞周期阻滞及抑制Akt/NF-κB信号增强维奈托克对AML细胞的杀伤作用。
AIM:This study aims to investigate the synergistic cytotoxic effects of chrysin and venetoclax on acute myeloid leukemia(AML)cells and to elucidate the underlying mechanisms.METHODS:Human AML cell lines MV411 and MOLM13 were cultured in vitro and treated with chrysin in combination with venetoclax.Cell viability was assessed using the CCK8 assay,while flow cytometry was employed to measure cell cycle distribution and apoptosis rates.Western blot was used to detect the expression of apoptosis-related proteins and protein kinase B(PKB/Akt)/nuclear factor-κB(NF-κB)signaling pathway-related proteins.RESULTS:The results from the CCK8 assay and flow cytometry demonstrated that treatment with 16 and 32μmol/L chrysin significantly inhibited the viability of AML cells and increased the proportion of cells in G1 phase,as well as the apoptosis rate.Notably,the cells in combination treatment group exhibited a marked reduction in proliferation and an elevated apoptosis rate compared with either chrysin or venetoclax group alone.Western blot analysis indicated that increasing concentrations of chrysin led to an elevation in cleaved poly(ADP-ribose)polymerase(PARP)level,alongside a down-regulation of proteins associated with the Akt/NF-κB signaling pathway.Furthermore,the combination treatment significantly up-regulated cleaved PARP level and down-regulated Akt/NF-κB pathway-related proteins compared with the treatment with chrysin or venetoclax alone.CONCLUSION:Chrysin and venetoclax synergistically inhibit the proliferation of AML cells and promote apoptosis by modulating the Akt/NF-κBsignaling pathway.
作者
王艳
朱沛雄
杨彭月
吴秀丽
李扬秋
余锡宝
徐玲
WANG Yan;ZHU Peixiong;YANG Pengyue;WU Xiuli;LI Yangqiu;YU Xibao;XU Ling(Institute of Hematology,School of Medicine,Key Laboratory of Regenerative Medicine of Ministry of Education,Jinan University,Guangzhou 510632,China;Key Laboratory of Viral Pathogenesis&Infection Prevention and Control of the Ministry of Education,Jinan University,Guangzhou 510632,China)
出处
《中国病理生理杂志》
北大核心
2025年第7期1300-1307,共8页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.82200167)
广东省基础与应用基础研究基金资助项目(No.2021A1515110140)
广东省大学生创新创业训练计划支持项目(No.S202310559081)
广州科技GI青年博士“启航”项目(No.2025A04J3702)。
