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作 者:赵丽凤 刘丽[1] 谭余庆[1] ZHAO Lifeng;LIU Li;TAN Yuqing(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing,100700,China)
出 处:《肿瘤药学》2020年第5期531-535,551,共6页Anti-Tumor Pharmacy
基 金:中央级公益性科研院所基本科研业务费专项资金资助(ZZ13-YQ-054)。
摘 要:目的观察三氧化二砷对人急性单核细胞白血病SHI-1细胞增殖和凋亡的影响,并探究其作用机制。方法取对数生长期SHI-1细胞,用1、2、4、8、16μmol·L-1三氧化二砷分别培养24、48、72h。MTT分别检测24、48、72h后细胞的增殖情况;Annexin V-FITC/PI双染法检测48h后的细胞凋亡率;Western blotting检测48h后Bax、Bcl-2、Caspase-3、Cleaved Caspase-3、Caspase-8和Caspase-9蛋白的表达情况。结果与对照组(0μmol·L-1)相比,三氧化二砷能显著抑制SHI-1细胞的增殖(P<0.05);作用48 h后,SHI-1细胞的凋亡比例随三氧化二砷浓度的升高而增加(P<0.05);随着三氧化二砷浓度的增加,Bcl-2/Bax比值降低,Caspase-3和Caspase-8蛋白表达水平显著降低(P<0.001),Cleaved Caspase-3蛋白表达水平显著升高(P<0.001),而Caspase-9蛋白表达水平无明显变化(P>0.05)。结论三氧化二砷可显著抑制急性单核细胞白血病SHI-1细胞的增殖并诱导其凋亡,其作用机制可能与Bcl-2/Bax比值降低,Caspase-3和Caspase-8的激活有关。Objective To investigate the effects of arsenic trioxide(ATO)on proliferation and apoptosis of acute monocytic leukemia SHI-1 cells,and to study the mechanism of apoptosis.Methods The SHI-1 cells in logarithmic phase were treated with different concentrations(1,2,4,8,16μmol·L-1)of ATO for 24 h,48 h and 72 h respectively.MTT was applied to detect the effects of ATO on the proliferation of SHI-1 cells after 24 h,48 h,72 h.Annexin V-FITC/PI was used to detect the changes of SHI-1 apoptosis after 48 h.Western blotting was performed to assess the expressions of Bax,Bcl-2,caspase-3,cleaved caspase-3,caspase-8 and caspase-9 after 48 h.Results The results of MTT showed that arsenic trioxide inhibited the proliferation of SHI-1 cells when compared with the control group(0μmol·L-1)(P<0.05).Annexin V-FITC/PI test results showed that apoptosis ratio of SHI-1 cells was increased along with the rise of ATO concentrations after 48 h treatment(P<0.05).Western blotting results confirmed that the Bcl-2/Bax expression ratio and the expressions of caspase-3 and caspase-8 were decreased(P<0.001),but the expression of cleaved caspase-3 was increased(P<0.001)along with the rise of ATO concentrations.The expression of caspase-9 did not show obvious changes(P>0.05).Conclusion Arsenic trioxide could significantly inhibit the proliferation and induce the apoptosis of acute monocytic leukemia cell SHI-1,and its mechanism may be related to the reduction of Bcl-2/Bax and activation of caspase-3 and caspase-8.
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