阿伐他汀对白血病细胞HL-60增殖和凋亡的影响及其信号通路机制  

Effects of Atorvastatin on Proliferation and Apoptosis of Leukemia Cell Line HL-60 and Its Mechanism of Signal Pathway

作　　者：戴静[1] 刘涛[1] 王凯[1] 庞迎旭 王琼[1] 陈珍珠[1] 

机构地区：[1]周口市中心医院血液内科,河南周口466000

出　　处：《中国实验血液学杂志》2017年第2期403-407,共5页Journal of Experimental Hematology

摘　　要：目的:探讨阿伐他汀对白血病细胞HL-60增殖和凋亡的影响及信号通路机制。方法:将培养获得的对数生长期的白血病细胞HL-60接种在96孔板,分别给予1、5和10μmol/L浓度的阿伐他汀,然后放入培养箱中(37℃,5%CO_2)培养(12、24和48 h),用MTT比色法检测白血病细胞的增殖能力。用流式细胞术检测白血病细胞的凋亡变化;RT-PCR法检测PI3K、ATK、mTOR基因mRNA表达水平;Western blot法检测PI3K、ATK、mTOR蛋白表达水平。实验设置空白对照组和阴性对照组。结果:阿伐他汀能够抑制HL-60细胞的增殖,浓度为10μmol/L的阿伐他汀作用48 h后对HL-60细胞的增殖抑制作用最强,其抑制率为(39.78±3.00)%,与阴性对照组比较,其差异有统计学意义(t=4.015,P<0.05);对HL-60细胞凋亡的诱导作用最强,其凋亡率为(43.30±3.92)%,与阴性对照组比较,其差异有统计学意义(t=3.624,P<0.05)。同时,阿伐他汀作用48 h后PI3K、ATK、mTOR基因表达水平均有所下降,其中10μmol/L浓度的阿伐他汀作用最为明显,分别下降了(37.04±4.15)%、(53.81±3.25)%和(40.62±2.41)%。与阴性对照组比较,其差异有统计学意义(t=4.806、3.800、4.313,P<0.05)。结论:阿伐他汀可能通过抑制PI3K/ATK/mTOR信号通路,实现对HL-60细胞增殖的抑制并且诱导其凋亡。Objective： To investigate the effect of atorvastatin on proliferation and apoptosis of leukemia cell line HL-60 and its mechanism of signal pathway. Methods： The leukemia HL-60 cells in logarithmic growth phase were seeded in 96 well plates and were treated with 1, 5 and 10 mol/L atorvastatin, then were cultured in the incubator （ at 37 ℃, 5% CO2 ） for 12 h, 24 h, 48 h. MTT colorimetric method was used to detect the proliferation leukemia cells, the apoptosis of leukemia cells was detected by flow cytometry; the expresion levels of phosphatidylinositol 3-kinase （PI3K）, serine threonine protein kinase（ATK） and mTOR at mRNA and protein levels were detected by RT-PCR and Western blot respectively. The experiments included blank control group, the negative control group and drug-treated group. Results： Atorvastatin could inhibit the proliferation of HL-60 cells. The treatment of HL-60 cells with 10 mol/L atorvastatin for 48 hours showed the strongest inhibition rate （ 39. 78 ＋ 3. 00 ） % which was statistically significant different from negative control group （t =4.015, P 〈 0.05） and the strongest induction-apoptosis effect on HL-60 cells （43.30 ±3.92） %, that was statistically significantly different from negative control group （ t = 3. 624, P 〈 0.05 ）. After treatment with atorvastatin for 48 hours, the expression levels of PI3 K, ATK and roTOR were decreased, in which the effect of 10 mol/L atorvastatin was the most obvious; The expression levels of PI3K, ATK and roTOR were decreased by （37.04 ±4.15） %, （53.81 ±3.25 ） % and （40.62 ±2.41 ） respectively, significantly different from the negative control （t = 4. 806,3. 800,4.313, P 〈 0.05）. Conclusion： Atorvastatin may inhibit the proliferation of HL-60 cells and induce apoptosis by inhibiting the PI3K/ATK/mTOR signaling pathway.

关 键 词：白血病 HL-60细胞 阿伐他汀 细胞增殖 细胞凋亡 

分 类 号：R733.7[医药卫生—肿瘤] R979.1[医药卫生—临床医学]