【摘要】 目的研究高三尖杉酯碱+阿糖胞苷+粒细胞集落刺激因子(HAG)联合地西他滨对骨髓增生异常综合征(MDS)患者凋亡自噬相关基因表达的影响。方法 MDS患者86例随机分为HAG组和联合组,每组43例。HAG组给予高三尖杉酯碱+阿糖胞苷+粒细胞集落刺激因子治疗。联合组在HAG组治疗基础上加用地西他滨治疗。比较2组骨髓单个核细胞(BMMNC)增殖相关基因(Ki67、PCNA、CDK2)、凋亡相关基因(Bcl-2、Bax、Caspase-3)、自噬相关基因(LC3、Beclin1)及磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/哺乳动物雷帕霉素靶蛋白(mTOR)通路关键蛋白表达变化。结果 2组治疗前Ki67、PCNA、CDK2、Bcl-2、Bax、Caspase-3、LC3、Beclin1蛋白表达及p-PI3K/PI3K、p-AKT/AKT、p-mTOR/mTOR比较差异无统计学意义(P>0.05);2组治疗后Ki67、PCNA、CDK2、Bcl-2蛋白表达及p-PI3K/PI3K、p-AKT/AKT、p-mTOR/mTOR均较治疗前显著降低(P<0.05),Bax、Caspase-3、LC3、Beclin1蛋白表达均较治疗前显著升高(P<0.05),且联合组Ki67、PCNA、CDK2、Bcl-2蛋白表达及p-PI3K/PI3K、p-AKT/AKT、p-mTOR/mTOR低于HAG组(P<0.05),Bax、Caspase-3、LC3、Beclin1蛋白表达高于HAG组(P<0.05)。结论 HAG联合地西他滨可能通过调控相关基因表达抑制MDS细胞增殖,并诱导其凋亡自噬,机制可能与下调PI3K/AKT/mTOR活性有关。更多还原

【Abstract】 Objective To investigate the effects of HAG combined with decitabine on the expressions of apoptosis and autophagy related genes in patients with myelodysplastic syndrome(MDS).Methods A total of 86 patients with MDS who were admitted and treated in our hospital from February 2014 to January 2015 were enrolled in the study, who were randomly divided into HAG group(n=43) and combination group(n=43). The patients in HAG group were treated by homoharringtonine+cytarabine+granulocyte colony stimulating factor(BMMNC),however, thepatients in combination group, on the basis of HAG group, were treated by decitabine. The expression levels of proliferation related genes(Ki67, PCNA and CDK2), apoptosis related genes(Bcl-2, Bax and Caspase-3), autophagy related genes(LC3 and Beclin1) and PI3 K/AKT/mTOR pathway key proteins in bone marrow mononuclear cells(BMMNC) were observed and compared between the two group.Results Before the treatment, there were no significant differences in the expression levels of Ki67, PCNA, CDK2, Bcl-2, Bax, Caspase-3, LC3, Beclin1 and p-PI3 K/PI3 K, p-AKT/AKT, p-mTOR/mTOR between the two groups(P>0.05). After treatment, the expression levels of Ki67, PCNA, CDK2, Bcl-2 and p-PI3 K/PI3 K, p-AKT/AKT, p-mTOR/mTOR in both groups were significantly decreased(P<0.05),however, the expression levels of Bax, Caspase 3, LC3 and Beclin1 in both groups were significantly increased(P<0.05). Moreover after treatment the expression levels of Ki67, PCNA, CDK2, Bcl-2 and p-PI3 K/PI3 K, p-AKT/AKT, p-mTOR/mTOR in combination group were significantly lower than those in HAG group(P<0.05),but the expressions levels of Bax, caspase-3, LC3 and Beclin1 in combination group were significantly higher than those in HAG group(P<0.05).Conclusion HAG combined with decitabine can inhibit cell proliferation, promote apoptosis and autophagy of MDS cells by regulating the expression of related genes, and itc action mechanism may be related to the down-regulation of the activities of PI3 K/AKT/mTOR.更多还原