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Archive > Volume 20 Issue 5 > 2013,20(5):575-579. DOI:10.3872/j.issn.1007-385X.2013.05.012 Prev Next
Basic Research
Influence of metformin on proliferation and apoptosis of acute promyelocytic leukemia NB4 cells
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Abstract:
Objective:To investigate the effect of metformin on the proliferation and apoptosis of acute promyelocytic leukemia (APL) NB4 cells and the possible mechanism. Methods: After the treatment of metformin alone or in combination with daunorubicin, MTT assay and flow cytometry were used to detect the proliferation and apoptosis of NB4 cells, respectively. The activation of apoptosis-related proteins caspase-3 and caspase-9 was determined by Western blotting. Results: Metformin inhibited proliferation of NB4 cells in a dose-dependent (r=0.952, P<0.01) and time-dependent (r=0.967, P<0.01) manner. After metformin treatment for 72 h, its IC50 value to NB4 cells was (6.39±0.37) mmol/L. Metformin increased the chemosensitivity of NB4 cells to daunorubicin. The inhibitory rate of NB4 cell proliferation in 0.625 mmol/L metformin and 0.02 μmol/L daunorubicin combination group was significantly higher than that in daunorubicin used alone group (\[29.84±0.21\]% vs \[10.68±0.45\]%, P<0.05). After the treatment of 5 mmol/L metformin for 48 h, the apoptotic rate of NB4 cells was significantly increased compared with that of the control group (\[43.95±0.29\]% vs \[7.12±0.29\]%，P<0.01). The expressions of activated caspase-3 and caspase-9 fragments were up-regulated after metformin treatment.Conclusion: Metformin can efficiently inhibit the proliferation, promote the apoptosis of NB4 cells, and enhance the chemosensitivity of NB4 cells to daunorubicin. Caspase-3 and caspase-9 may be involved in the NB4 cell apoptosis induced by metformin.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 81101786), and the “Six Top Talents” Foundation of Jiangsu Province (No. 2011-ws-062)
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