本研究探讨羟甲基戊二酸单酰辅酶A还原酶抑制剂辛伐他汀对人急性单核细胞白血病株( SHI-1)细胞增殖和凋亡的影响及PI3K/AKT通路变化.取对数生长期细胞,实验分为阴性对照组和辛伐他汀处理组(终浓度分别为5、10、15 μ mol/L),培养24、48、72 h.采用MTT法观察SHI-1细胞增殖能力；流式细胞术测定SHI-1细胞凋亡指标变化；PCR芯片研究SHI-1细胞pI3 K/AKT通路84个特异性基因mRNA的差异表达.结果表明,辛伐他汀对SHI-1细胞有明显抑制增殖和促凋亡作用,呈时间与剂量依赖性.15 μmol/L辛伐他汀处理SHI-1细胞24、48、72h,细胞增殖抑制率分别为26.82％、47.09％、63.92％,细胞早期凋亡率分别为5.73％、13.25％、15.59％.与对照组相比,15 μmol/L辛伐他汀处理SHI-1细胞48 h组中有39个基因表达发生改变,其中26个基因表达下调、13个基因表达上调.结论:辛伐他汀能抑制SHI-1细胞增殖并诱导其凋亡,其诱导凋亡机制可能与辛伐他汀调节PI3K/AKT通路相关基因的表达有关.%To investigate the effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvatalin( SV) on proliferation, apoptosis and the PBK/AKT signaling pathway in human acute monocytic leukemia cell line SHI-1. SHI-1 cells were incubated with different concentrations of SV (5, 10,15 μmol/L). Otherwise, SHI-1 cells without any treatment were used as control. Cells in different groups were collected at 24, 48 and 72 h after incubation for further detection. MTT method was used to assay the growth inhibition rate and flow cytometry was used to detect the early stage apoptosis ratio. The human PDK-AKT Signaling Pathway RT2 Profiler? PCR Array was used to detect the expression of 84 genes involved in PDK-AKT signaling. The results indicated that the SV inhibited the proliferation and inducted the apoptosis of SHI-1 cells in time- and dose-dependent manners significantly. The growth inhibition rates of SHI-1 cells treated with 15 μmol/L SV for 24,48 and 72 h were 26. 82% , 47.09% and 63.92% , respectively; and their early stage apoptosis ratios were 5.75% , 13.25% and 15.59%, respectively. Compared with the control group, expression levels of 39 genes were changed in the group of 15 μmol/L SV at 48 h, among them 26 genes were down-regulated and 13 genes were up-regulated. It is concluded that the SV can inhibit proliferation and induce apoptosis of SHI-1 cells, and the mechanism may be associated with the changes of gene expression level in PI3K-AKT signaling pathway regulated by SV.
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