摘要
目的探索重楼皂苷Ⅰ对骨髓瘤细胞凋亡的作用及其机制。方法采用人骨髓瘤细胞株RPMI-8226、U266,分为对照组和0.25、0.5、1μmol·L^(-1)重楼皂苷Ⅰ组,MTT法检测细胞存活率,流式细胞术检测细胞凋亡率,Western blot法检测凋亡相关蛋白表达,AutoDock 4.0软件将UHRF1和重楼皂苷Ⅰ进行分子对接。结果与对照组相比,重楼皂苷Ⅰ组骨髓瘤细胞存活率显著降低(P<0.05),呈浓度和时间依赖性趋势;凋亡率显著上升(P<0.05),caspase-3、caspase-7、caspase-9蛋白表达降低(P<0.05),cleaved-caspase-3、cleaved-caspase-7、cleaved-caspase-9、PARP、cleaved-PARP蛋白表达增加(P<0.05),UHRF1蛋白表达降低(P<0.05)。分子对接显示UHRF1可与重楼皂苷Ⅰ结合,结合能为-6.95 kcal·mol-1。结论重楼皂苷Ⅰ可通过UHRF1促进骨髓瘤细胞凋亡发挥抗骨髓瘤作用。
AIM To explore the effects of polyphyllin I on apoptosis of myeloma cells and its molecular mechanisms.METHODS Human myeloma cell RPMI-8226 and U266 cell lines were divided into control group and 0.25,0.5,1μmol·L^(-1)polyphyllin I groups.Cell survival rate were measured by MTT.Cell apoptosis rate was detected by flow cytometry and apoptosis-related protein expression was detected by Western blot.UHRF1 and polyphyllin I were molecular docking by Auto Dock 4.0 software.RESULTS Compared with the control group,the survival rates of myeloma cells in polyphyllin I groups were significantly reduced with concentration and time-dependent trend(P<0.05).The apoptosis rates were increased significantly(P<0.05).The expressions of caspase-3,caspase-7,caspase-9 proteins were decreased(P<0.05),and the expressions of cleaved-caspase 3,cleaved-caspase 7,cleaved-caspase 9,PARP,cleaved-PARP proteins were increased P<0.05).UHRF1 protein express were reduced(P<0.05).Molecular docking showed that UHRF1 could bind with polyphyllin I with binding energy of-6.95 kcal·mol^(-1).CONCLUSION Polyphyllin I can play an anti-myeloma effect by promoting apoptosis of myeloma cells through UHRF1.
作者
王彦敏
伏瑶
全艳春
王丽娟
WANG Yan-min;FU Yao;QUAN Yan-chuan;WANG Lijua(Linyi People's Hospital Cultivation Base,JinZhou Medical University,Linyin SHANDONG 276000,China;Central Laboratory,Linyi People's Hospital,Linyin SHANDONG 276000,China;Department of Hematology,Linyi People's Hospital,Linyin SHANDONG 276000,China;Linyi Key Laboratory of Tumor Biology,Linyin SHANDONG 276000,China)
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2023年第7期462-466,共5页
Chinese Journal of New Drugs and Clinical Remedies
基金
国家自然科学基金(81402353)
中国博士后科学基金(2020M672105)
山东省重点研发计划(2018GSF118035)
山东省自然科学基金青年基金(ZR2022QH168)
山东省医药卫生科技发展计划项目(202002040822)
徐州医科大学附属医院发展基金(XYFM2020016,XYFY2020040)。