CAJ | 학술논문

目的探讨羟甲基戊二酸单酰辅酶A(HMG-CoA)还原酶的抑制剂辛伐他汀(SV)联合佛波酯(PMA)对SHI-1细胞增殖，分化与凋亡的影响，以及WT1/hDMP1基因的表达变化。方法以不同浓度辛伐他汀单独或联合PMA处理SHI-1细胞，取对数生长期细胞进行实验。各组细胞分别进行MTT法观察细胞增殖能力；流式细胞测定SHI-1细胞凋亡指标Annexin吁/propidium iodide变化； Real-time RT-PCR测定WT1/hDMP1基因表达变化。结果15μmol/LSV，10μmol/LSV单独处理SHI-1细胞，随着培养时间延长，细胞抑制率增加(F=24.61，=0.000)，AnnexinV表达水平逐渐增高(F=5.69，=0.018)，WT1表达水平逐渐降低(F=12.20,=0.008)，同时伴随着hDMP1表达水平的增加(F=23.81,=0.000)，其中以15μmol/LSV联合PMA处理SHI-1细胞培养72h细胞抑制率最为明显。结论辛伐他汀体外抑制SHI-1细胞的增殖，促进SHI-1细胞的分化及凋亡，降低WT1表达，升高hDMP1表达，提示辛伐他汀具有协同治疗急性单核细胞白血病的潜能。
목적탐토간갑기무이산단선보매A(HMG-CoA)환원매적억제제신벌타정(SV)연합불파지(PMA)대SHI-1세포증식，분화여조망적영향，이급WT1/hDMP1기인적표체변화。방법이불동농도신벌타정단독혹연합PMA처리SHI-1세포，취대수생장기세포진행실험。각조세포분별진행MTT법관찰세포증식능력；류식세포측정SHI-1세포조망지표Annexin우/propidium iodide변화； Real-time RT-PCR측정WT1/hDMP1기인표체변화。결과15μmol/LSV，10μmol/LSV단독처리SHI-1세포，수착배양시간연장，세포억제솔증가(F=24.61，=0.000)，AnnexinV표체수평축점증고(F=5.69，=0.018)，WT1표체수평축점강저(F=12.20,=0.008)，동시반수착hDMP1표체수평적증가(F=23.81,=0.000)，기중이15μmol/LSV연합PMA처리SHI-1세포배양72h세포억제솔최위명현。결론신벌타정체외억제SHI-1세포적증식，촉진SHI-1세포적분화급조망，강저WT1표체，승고hDMP1표체，제시신벌타정구유협동치료급성단핵세포백혈병적잠능。
Objective To investigate the ef ect of Simvastatin (SV) combined with Phorbol-12-myristate-13-acetate (PMA) on the proliferation ,dif erentiation,apoptosis and WT1/hDMP1 gene expression profiles of human monocytic leukemia cellline SHI-1. Methods SHI-1 cells were incubated with Simvastatin and PMA solely or in combination,cells of dif erent groups were col ected after incubation for further detection.M'IT method was used to assay the growth inhibition rate and cytoflowmetry was used to detect the early stage apoptosis ratio and cellnecrosis ratio.Real-time quantitative reverse transcriptase polymerase chain reaction(RT-PCR) was used to detect the WT1/hDMP1 gene expression levels. Results Treated with 15μmol/LSV and 10μmol/LSV in each, with the SHI-1 cells growth, the cellinhibition rates gradual y increased( =24.61, =0.000), and AnnexinV expression levels( =5.69, =0.018), however the WT1 expression levels gradual y decreased ( =12.20, =0.008),paral eled with hDMP1 expression levels increased in reverse ( =23.81, =0.000),furthermore the SHI-1 cells treated with Combination of 15μmol/LSV with 5ng/L PMA displayed obvious interaction for cellgrowth inhibition and Annexin V expression were found. Conclusion Simvastatin in vitro inhibited SHI-1 cellproliferation, induced celldifferentiation and promoted cellapotosis, as wel as decreased the WT1 expression and increased hDMP1 expression dose-dependently, indicating that simvastatin has the synergistic anti-monocytic potency in vitro.