维奈托克对急性髓系白血病肿瘤标志基因和炎症因子的影响

Effect of Venetoclax on Tumor Associated Genes and Cytokines in Acute Myeloid Leukemia

目的观察维奈托克对急性髓系白血病(AML)外周血淋巴细胞RNA和炎症因子的影响。方法采用噻唑蓝(MTT)法检测维奈托克的最适浓度及AML细胞凋亡情况,实时定量聚合酶链反应检测维奈托克作用前后AML患者外周血免疫细胞标志mRNA的表达水平变化,酶联免疫吸附(ELISA)检测炎症因子的变化。结果 300 nmol·L-1维奈托克显著降低AML患者外周血单核细胞恶性肿瘤相关基因BCL-2、SIRPα、CD47、PDL-1、PDL-2、EZH2的表达(P<0.05或P<0.01),并促进免疫反应活化分子TRAIL和肿瘤坏死因子(TNF)-α的表达(P<0.01)。ELISA检测结果显示TNF-α和干扰素-γ释放量显著升高。结论维奈托克可以调控肿瘤相关基因并促进免疫细胞释放炎症因子,从而促进AML肿瘤细胞凋亡。

ObjectiveTo investigate the effect of venetoclax on RNA expression and cytokines release in lymphocytes isolated from acute myeloid leukemia(AML)patients.MethodsMTT method was performed to study the apoptosis of AML cells and optimize the concentration of venetoclax.The gene markers expression and cytokines production before and after venetoclax treatment were examined by RT PCR and ELISA methods,respectively.ResultsAfter chemotherapy,the expression of tumor associated inhibitory genes including BCL2(P<0.05),SIRPα(P<0.05),CD47(P<0.05),PDL1(P<0.05),PDL2(P<0.01),and EZH2(P<0.05)were significantly decreased when venetoclax reached300nmol·L-1.In addition,the expression levels of the activated molecules significantly increased,such as TRAIL(P<0.01)and TNF-α(P<0.01).The ELISA results showed that the release of human TNF-αand IFN-γhave significantly increased.ConclusionVenetoclax,which is a chemotherapeutic drug,can be used as tumor targeting drug.It can promote apoptosis in AML patients by regulating the genes expressions related to malignancy and cytokines production.