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目的:探讨二甲双胍对急性早幼粒细胞白血病(acute promyelocytic leukemia,APL)NB4细胞增殖与凋亡的影响及其可能的机制。方法:二甲双胍单独或联合多柔比星处理NB4细胞后,采用MTT法检测NB4细胞的增殖,采用流式细胞术检测细胞的凋亡,采用Western blotting法检测凋亡相关蛋白caspase-9及caspase-3的活化。结果:二甲双胍可剂量(r=0.952,P<0.01)和时间(r=0.967,P<0.01)依赖性抑制NB4细胞的增殖,处理72 h后,其对NB4细胞的IC50值为(6.39±0.37)mmol/L。二甲双胍可增加NB4细胞对多柔比星的化疗敏感性,0.625 mmol/L二甲双胍联合0.02μmol/L的多柔比星对NB4细胞的增殖抑制率明显高于单用多柔比星组[(29.84±0.21)%vs(10.68±0.45)%,P<0.05]。5 mmol/L二甲双胍处理48 h后,NB4细胞的凋亡率明显高于未处理对照组[(43.95±0.29)%vs(7.12±0.29)%,P<0.01];二甲双胍处理NB4细胞后,凋亡蛋白caspase-3、caspase-9活化片段表达上调。结论:二甲双胍能够有效抑制APL细胞株NB4的增殖、促进其凋亡,并能增强其对多柔比星的化疗敏感性,caspase-3和caspese-9凋亡蛋白可能参与二甲双胍诱导NB4细胞凋亡的过程。
Objective: To investigate the effect of metformin on proliferation and apoptosis of NB4 cells in acute promyelocytic leukemia (APL) and its possible mechanism. Methods: NB4 cells were treated with metformin alone or in combination with doxorubicin. The proliferation of NB4 cells was detected by MTT assay. The apoptosis of NB4 cells was detected by flow cytometry. The expressions of caspase-9 and caspase- 3 activation. Results: Metformin inhibited the proliferation of NB4 cells dose dependently (r = 0.952, P <0.01) and time (r = 0.967, P <0.01), and the IC50 value of NB4 cells was (6.39 ± 0.37 ) mmol / L. Metformin increased the chemosensitivity of NB4 cells to doxorubicin, and the inhibitory rate of 0.625 mmol / L metformin combined with 0.02 μmol / L doxorubicin on NB4 cells was significantly higher than that of doxorubicine alone group [(29.84 ± 0.21)% vs (10.68 ± 0.45)%, P <0.05]. The apoptosis rate of NB4 cells treated with 5 mmol / L metformin for 48 h was significantly higher than that of untreated control group [(43.95 ± 0.29)% vs (7.12 ± 0.29)%, P <0.01]. After metformin treatment, The expressions of caspase-3 and caspase-9 were up-regulated. CONCLUSION: Metformin can effectively inhibit the proliferation and promote the apoptosis of APL cell line NB4 and enhance its chemosensitivity to doxorubicin. The apoptosis proteins of caspase-3 and caspese-9 may be involved in metformin-induced NB4 cell apoptosis the process of.