关键词:

白血病, 细胞凋亡, cMyc 抑制剂10058?F4, DNA 损伤

Abstract:

Objective To investigate the effect and molecular mechanism of cMyc inhibitor 10058⁃F4 onleukemia THP1 cells. Methods Human leukemic THP1 cells were cultured in vitro and treated with differentconcentrations（1，5，10，50，100 μmol/L）of cMyc inhibitor 10058⁃F4. The effect of cell growth inhibition wasmeasured by CCK ⁃8 assays. The changes of apoptosis and mitochondrial membrane potential were measured by Calcein/PI and JC ⁃1 fluorescence staining，respectively. The cell cycle was determined by flow cytometry. Theexpression levels of apoptosis ⁃ related proteins（Cleaved ⁃Caspase ⁃3 and Bax）and DNA damage response ⁃ relatedproteins（pATM and γH2AX）were analyzed by Western blot. Results Different concentrations of 10058⁃F4significantly inhibited THP1 cell proliferation in concentration⁃dependent and time⁃dependent manners. 10058⁃F4induced apoptosis and reduced mitochondrial membrane potential levels in a concentration⁃dependent way，and thedifference was statistically significant（P < 0.05）. Cell cycle assays showed that 10058⁃F4 could induce phase G2/M arrests in THP1 cells. Western blot experiments showed that the expression of the apoptotic（Cleaved⁃Caspase⁃3and Bax）and DNA damage related proteins（pATM and γH2AX）were significantly increased in THP1 cells treat⁃ed with 10058⁃F4，and the difference was statistically significant（P < 0.05）. Conclusions The cMyc inhibitor10058⁃F4 could induce the apoptosis of leukemic THP1 cells by inducing cellular DNA damage and activating rele⁃vant signal pathways.

Key words:

leukaemia, apoptosis, cMyc inhibitor 10058?F4, DNA damage