白血病·淋巴瘤
白血病·淋巴瘤
백혈병·림파류
JOURNAL OF LEUKEMIA & LYMPHOMA
2011年
12期
726-729
,共4页
贺白%邱国强%江庭秀%顾伟英%王志林%吴浩清%华晓莹%吴炜%董伟民%刘佳
賀白%邱國彊%江庭秀%顧偉英%王誌林%吳浩清%華曉瑩%吳煒%董偉民%劉佳
하백%구국강%강정수%고위영%왕지림%오호청%화효형%오위%동위민%류가
白血病,实验性%辛伐他汀%NB4细胞%全反式维甲酸%细胞增殖%细胞分化%细胞凋亡
白血病,實驗性%辛伐他汀%NB4細胞%全反式維甲痠%細胞增殖%細胞分化%細胞凋亡
백혈병,실험성%신벌타정%NB4세포%전반식유갑산%세포증식%세포분화%세포조망
Leukemia,experimental%Simvastatin%NB4 cell%All-trans retinoic acid%Cell proliferation%Cell differentiation%Apoptosis
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)对人类急性早幼粒细胞白血病细胞株NB4增殖、分化与凋亡的影响.方法 以不同浓度SV联合全反式维甲酸( ATRA) 0.5 μmol/L处理NB4细胞,取对数生长期各组细胞分别进行细胞形态观察；四甲基偶氮唑蓝比色( MTT)法观察细胞增殖能力；流式细胞术测定NB4细胞分化指标CD11b和细胞凋亡指标Annexin V/propidium iodide的变化.结果 15、10、5μmol/L SV单独处理NB4细胞,随着培养时间延长,细胞抑制率提高(F=7.15,P=0.000),CD11b的表达水平逐渐升高(F=3.41,P=0.014),AnnexinV表达水平逐渐增高(F=43.38,P=0.000),其中以15tμmol/L SV组NB4细胞变化最明显,培养72 h细胞抑制率为(0.96±0.02)％,CD11b表达水平(62.41±6.37)％,AnnexinV表达水平(87.38±2.94)％.3组浓度SV联合ATRA对NB4细胞抑制率和AnnexinV表达水平差异无统计学意义,但协同促进NB4细胞CD11b表达水平升高.15 μmol/L SV联合ATRA处理NB4细胞培养72 h,CD11b表达水平为(89.46±9.13)％,较ATRA和SV单药处理组的(71.27±7.27)％和(62.41±6.37)％明显升高(t=2.71,P=0.054;t=4.37,P=0.017),两药合用具有明显交互作用(F=4.093,P=0.025).结论 SV以剂量依赖方式体外抑制NB4细胞增殖,促进凋亡,与ATRA协调诱导NB4细胞的分化,提示SV具有协同治疗急性早幼粒细胞白血病的潜能.
目的 探討羥甲基戊二痠單酰輔酶A( HMG-CoA)還原酶的抑製劑辛伐他汀(SV)對人類急性早幼粒細胞白血病細胞株NB4增殖、分化與凋亡的影響.方法 以不同濃度SV聯閤全反式維甲痠( ATRA) 0.5 μmol/L處理NB4細胞,取對數生長期各組細胞分彆進行細胞形態觀察；四甲基偶氮唑藍比色( MTT)法觀察細胞增殖能力；流式細胞術測定NB4細胞分化指標CD11b和細胞凋亡指標Annexin V/propidium iodide的變化.結果 15、10、5μmol/L SV單獨處理NB4細胞,隨著培養時間延長,細胞抑製率提高(F=7.15,P=0.000),CD11b的錶達水平逐漸升高(F=3.41,P=0.014),AnnexinV錶達水平逐漸增高(F=43.38,P=0.000),其中以15tμmol/L SV組NB4細胞變化最明顯,培養72 h細胞抑製率為(0.96±0.02)％,CD11b錶達水平(62.41±6.37)％,AnnexinV錶達水平(87.38±2.94)％.3組濃度SV聯閤ATRA對NB4細胞抑製率和AnnexinV錶達水平差異無統計學意義,但協同促進NB4細胞CD11b錶達水平升高.15 μmol/L SV聯閤ATRA處理NB4細胞培養72 h,CD11b錶達水平為(89.46±9.13)％,較ATRA和SV單藥處理組的(71.27±7.27)％和(62.41±6.37)％明顯升高(t=2.71,P=0.054;t=4.37,P=0.017),兩藥閤用具有明顯交互作用(F=4.093,P=0.025).結論 SV以劑量依賴方式體外抑製NB4細胞增殖,促進凋亡,與ATRA協調誘導NB4細胞的分化,提示SV具有協同治療急性早幼粒細胞白血病的潛能.
목적 탐토간갑기무이산단선보매A( HMG-CoA)환원매적억제제신벌타정(SV)대인류급성조유립세포백혈병세포주NB4증식、분화여조망적영향.방법 이불동농도SV연합전반식유갑산( ATRA) 0.5 μmol/L처리NB4세포,취대수생장기각조세포분별진행세포형태관찰；사갑기우담서람비색( MTT)법관찰세포증식능력；류식세포술측정NB4세포분화지표CD11b화세포조망지표Annexin V/propidium iodide적변화.결과 15、10、5μmol/L SV단독처리NB4세포,수착배양시간연장,세포억제솔제고(F=7.15,P=0.000),CD11b적표체수평축점승고(F=3.41,P=0.014),AnnexinV표체수평축점증고(F=43.38,P=0.000),기중이15tμmol/L SV조NB4세포변화최명현,배양72 h세포억제솔위(0.96±0.02)％,CD11b표체수평(62.41±6.37)％,AnnexinV표체수평(87.38±2.94)％.3조농도SV연합ATRA대NB4세포억제솔화AnnexinV표체수평차이무통계학의의,단협동촉진NB4세포CD11b표체수평승고.15 μmol/L SV연합ATRA처리NB4세포배양72 h,CD11b표체수평위(89.46±9.13)％,교ATRA화SV단약처리조적(71.27±7.27)％화(62.41±6.37)％명현승고(t=2.71,P=0.054;t=4.37,P=0.017),량약합용구유명현교호작용(F=4.093,P=0.025).결론 SV이제량의뢰방식체외억제NB4세포증식,촉진조망,여ATRA협조유도NB4세포적분화,제시SV구유협동치료급성조유립세포백혈병적잠능.
Objective To investigate the effects of simvastatin (SV) on the proliferation,differentiation and apoptosis of human promyelocytic leukemia cell line NB4.Methods NB4 cells were incubated with SV at different concentration with or without all-trans retinoic acid (ATRA),and NB4 cells without any treatment were taken as normal control.Cells of different groups were collected at 24 h,48 h and 72 h after incubation for further detection.Morphological changes by Wright stain were performed.MTT method was used to assay the growth inhibition rate and flow cytometry was used to detect the surface CD11b expression levels,the early stage apoptosis ratio and cell necrosis ratio.Results Treated with 15 μ mol/L SV,10 μ mol/L SV and 5 μ mol/L SV respectively,with the NB4 cells growth,the cell inhibition rates gradually increased (F =7.15,P =0.000),as well as CD11b expression levels (F =3.41,P =0.014) and AnnexinVexpression levels (F =43.38,P =0.000).Furthermore the NB4 cells treated with 15 μ mol/L SV exhibited the most significant changes with cell inhibition rate of 0.96±0.02,CD11b expression level increased to (62.41±6.37) ％ and AnnexinV expression level increased to (87.38±2.94) ％ after 72 h incubation.Combination of 15 μmol/L SV with 0.5 μmol/L ATRA displayed obvious interaction for increasing CD11b expression levels (F =4.093,P =0.025),while no significant interaction for cell inhibition rates and Annexin V expression levels were observed.After 72 h incubation,the CD11b expression levels (89.46±9.13) ％ in NB4 cells treated with 15 μ mol/L SV in combination with 0.5 μ mol/L ATRA were significantly higher than those treated with ATRA (71.27±7.27) ％ and SV (62.41±6.37) ％ (t =2.71,P =0.054; t =4.37,P =0.017)' solely.Conclusion Simvastatin in vitro inhibits NB4 cell proliferation,promotes cell apoptosis,and synergistically induces cell differentiation with ATRA dose-dependently in vitro,which indicates that SV may have the effect of synergistic anti-promyelocytic potency with ATRA.
