二烯丙基二硫对人白血病HL-60细胞株增殖的影响及其机制探讨
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摘要
目的探讨二烯丙基二硫(diallyl disulfide,DADS)对人白血病HL-60细胞株增殖的影响及survivin蛋白表达的变化和细胞周期的改变之间的关系,从而探讨DADS的抗白血病机制。
方法采用MTT法观察DADS对体外培养的HL-60细胞增殖的影响;应用SP-免疫细胞化学法检测药物作用前后白血病HL-60细胞内survivin蛋白的含量;同时用流式细胞仪(FCM)检测细胞周期变化。
结果DADS对HL-60细胞具有明显的生长抑制效应。其对HL-60细胞的生长抑制率与药物浓度、时间有明显依赖关系(r＞0.9,P＜0.01)。0.625mg/LDADS干预HL-60细胞24小时,细胞生长抑制率为8.94%,随着浓度增加,时间延长,20.0mg/L的DADS作用HL-60细胞72小时后,细胞抑制率升高至70.66%。SP免疫组化显示空白对照组及DMSO溶媒对照组均有survivin蛋白的高表达,其染色强度指数(SII)分别为1125及1126,两者无显著性差异(P＞0.05)。5、10、20mg/L的DADS作用于HL-60细胞24、48及72小时能呈时间、浓度依赖性下调survivin蛋白的表达(r＞0.9,P＜0.01),20mg/L的DADS作用于HL-60细胞72小时,SII为119,survivin蛋白表达抑制最为明显。三个DADS浓度组间差异显著(P＜0.01),与空白对照组比较也有显著性差异(P＜0.01)。流式细胞仪检测结果提示,伴随着survivin蛋白的下调,DADS可呈浓度、时间依赖性阻滞细胞于G2/M期(r＞0.9,P＜0.01)。20mg/L的DADS作用于HL-60细胞72小时G2/M期细胞比例达最高峰,为66.56%。
结论DADS能明显抑制HL-60细胞的增殖;DADS下调survivin蛋白,并使HL-60细胞阻滞于G2/M期。
Objective To investigate the proliferation of human leukemic HL-60 cell line and the correlation between the expreesion of survivin protein and cell cycle treated by diallyl disulfide(DADS).
Method MTT was used to test the growth of HL - 60 cells treated by DADS;SP-immunohistochemical and flow cytometry were used to study the expression of survivin protein in HL-60 cells and cell cycle arrest treated by DADS.
Results DADS significantly inhibited the proliferation of HL - 60 cells and the inhibiting effects had a dose -time dependence(r＞0.9, p＜0.01).The inhibition fraction of HL - 60 cells rose from 8.94%to 70.66%with DADS increasing from 0.625mg/L for 24 hours to 20.0mg/ L for 72 hours.Survivin was expressed in blank control group and DMSO solvent group at very high level.Their SⅡare 1125 and 1126 respectively and the difference between them is not statistically significant(P＞0.05).The expression of survivin protein could be down regulated by 5,10,and 20mg/L DADS-treated HL-60 cells for 24、48 and 72 hours and the effects had a time-dose dependence(r＞0.9,p＜0.01).The SⅡof HL-60 cells treated by 20mg/L DADS for 72 hours is 119,which is the lowest level in the test.The differences in the DADS -treated HL-60 cells groups and the control group were all statistically significant (P＜0.01),there were also statistically significant differences among the three DADS -- treated HL-60 cells groups(P＜0.01).G2/M phase arrest witch is accompanied with the down-regulated of survivin protein could be found in DADS interference in a dose-time dependent manner (r＞0.9,P＜0.01)Treated with 20mg/L DADS for 72 hours,the percentage of cells in G2/M phase rose to the highest level of 66.56%.
Conclusion DADS can effectively inhibit the proliferation of HL-60 cells,down-regulate the level of survivin protein and bring about G2/M phase arrest.
方法采用MTT法观察DADS对体外培养的HL-60细胞增殖的影响;应用SP-免疫细胞化学法检测药物作用前后白血病HL-60细胞内survivin蛋白的含量;同时用流式细胞仪(FCM)检测细胞周期变化。
结果DADS对HL-60细胞具有明显的生长抑制效应。其对HL-60细胞的生长抑制率与药物浓度、时间有明显依赖关系(r＞0.9,P＜0.01)。0.625mg/LDADS干预HL-60细胞24小时,细胞生长抑制率为8.94%,随着浓度增加,时间延长,20.0mg/L的DADS作用HL-60细胞72小时后,细胞抑制率升高至70.66%。SP免疫组化显示空白对照组及DMSO溶媒对照组均有survivin蛋白的高表达,其染色强度指数(SII)分别为1125及1126,两者无显著性差异(P＞0.05)。5、10、20mg/L的DADS作用于HL-60细胞24、48及72小时能呈时间、浓度依赖性下调survivin蛋白的表达(r＞0.9,P＜0.01),20mg/L的DADS作用于HL-60细胞72小时,SII为119,survivin蛋白表达抑制最为明显。三个DADS浓度组间差异显著(P＜0.01),与空白对照组比较也有显著性差异(P＜0.01)。流式细胞仪检测结果提示,伴随着survivin蛋白的下调,DADS可呈浓度、时间依赖性阻滞细胞于G2/M期(r＞0.9,P＜0.01)。20mg/L的DADS作用于HL-60细胞72小时G2/M期细胞比例达最高峰,为66.56%。
结论DADS能明显抑制HL-60细胞的增殖;DADS下调survivin蛋白,并使HL-60细胞阻滞于G2/M期。
Objective To investigate the proliferation of human leukemic HL-60 cell line and the correlation between the expreesion of survivin protein and cell cycle treated by diallyl disulfide(DADS).
Method MTT was used to test the growth of HL - 60 cells treated by DADS;SP-immunohistochemical and flow cytometry were used to study the expression of survivin protein in HL-60 cells and cell cycle arrest treated by DADS.
Results DADS significantly inhibited the proliferation of HL - 60 cells and the inhibiting effects had a dose -time dependence(r＞0.9, p＜0.01).The inhibition fraction of HL - 60 cells rose from 8.94%to 70.66%with DADS increasing from 0.625mg/L for 24 hours to 20.0mg/ L for 72 hours.Survivin was expressed in blank control group and DMSO solvent group at very high level.Their SⅡare 1125 and 1126 respectively and the difference between them is not statistically significant(P＞0.05).The expression of survivin protein could be down regulated by 5,10,and 20mg/L DADS-treated HL-60 cells for 24、48 and 72 hours and the effects had a time-dose dependence(r＞0.9,p＜0.01).The SⅡof HL-60 cells treated by 20mg/L DADS for 72 hours is 119,which is the lowest level in the test.The differences in the DADS -treated HL-60 cells groups and the control group were all statistically significant (P＜0.01),there were also statistically significant differences among the three DADS -- treated HL-60 cells groups(P＜0.01).G2/M phase arrest witch is accompanied with the down-regulated of survivin protein could be found in DADS interference in a dose-time dependent manner (r＞0.9,P＜0.01)Treated with 20mg/L DADS for 72 hours,the percentage of cells in G2/M phase rose to the highest level of 66.56%.
Conclusion DADS can effectively inhibit the proliferation of HL-60 cells,down-regulate the level of survivin protein and bring about G2/M phase arrest.
引文
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