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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、15μmol/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PI3K/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。15μmol/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,15μmol/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。
This study was to investigate the effects of simvastatin, a inhibitor of hydroxymethyl glutaryl coenzyme A reductase, on the proliferation and apoptosis of human acute monocytic leukemia (SHI-1) cells and the changes of PI3K / AKT pathway. The logarithmic growth phase cells were divided into negative control group and simvastatin treatment group (final concentrations were 5,10,15μmol / L), cultured for 24,48,72 h. The proliferation of SHI-1 cells was observed by MTT assay. The apoptosis index of SHI-1 cells was determined by flow cytometry. The differential expression of 84 specific mRNAs of PI3K / AKT pathway in SHI-1 cells was detected by PCR. The results showed that simvastatin on SHI-1 cells significantly inhibited the proliferation and promote apoptosis in a time and dose-dependent manner. SHI-1 cells were treated with 15μmol / L simvastatin for 24,48,72h, the cell proliferation inhibition rates were 26.82%, 47.09% and 63.92%, respectively. The early apoptotic rates of SHI-1 cells were 5.73%, 13.25% and 15.59%, respectively. Compared with the control group, the expression of 39 genes changed in SHI-1 cells treated with 15μmol / L simvastatin for 48 h, of which 26 genes were down-regulated and 13 genes were up-regulated. Conclusion: Simvastatin can inhibit proliferation and induce apoptosis of SHI-1 cells. The mechanism of apoptosis induced by simvastatin may be related to the regulation of the expression of PI3K / AKT pathway by simvastatin.