Effect of chidamide combined with arsenic acid on the proliferation of T cell lymphoma Hut-78 cells and its mechanism / 白血病·淋巴瘤

ABSTRACT

Objective:To investigate the effect of chidamide combined with arsenic acid on the proliferation inhibitory of T cell lymphoma Hut-78 cells and its mechanism.Methods:Low concentration group included 1.0 μmol/L chidamide, 4.0 μmol/L arsenic trioxide or both of them (1.0 μmol/L chidamide + 4.0 μmol/L arsenic trioxide). High concentration group included 1.5 μmol/L chidamide, 6.0 μmol/L arsenic trioxide or both of them (1.5 μmol/L chidamide + 6.0 μmol/L arsenic trioxide). Both groups were used to treat Hut-78 cells for 24 h and 48 h, respectively. Cell proliferation of Hut-78 cells in all drug treatment groups was tested by using methyl thiazolyl tetrazolium (MTT) method, and the proliferation inhibitory rate was also calculated. The expressions of vascular endothelial growth factor (VEGR) and bcl-2 protein of Hut-78 cells in different drug treatment groups by using Western blotting.Results:The cell proliferation inhibitory rate of Hut-78 cells treated for 24 h of 1.0 μmol/L chidamide, 4.0 μmol/L arsenic trioxide or both of them (1.0 μmol/L chidamide+ 4.0 μmol/L arsenic trioxide) was (8.8±0.1)%, (9.2±0.5)% and (11.0±0.1)%, respectively ( F = 12.45, P < 0.05); The cell proliferation inhibitory rate of Hut-78 cells treated for 48 h was (19.1±0.5)%, (18.3±0.9)%, (23.1±1.3)%, respectively ( F = 9.86, P < 0.05). The cell proliferation inhibitory rate of Hut-78 cells treated for 24 h of 1.5 μmol/L chidamide, 6.0 μmol/L arsenic trioxide or both of them (1.5 μmol/L chidamide+ 6.0 μmol/L arsenic trioxide) was (15.4±0.9)%, (13.2±0.9)% and (18.2±1.1)%, respectively ( F = 7.06, P < 0.05); The cell proliferation inhibitory rate of Hut-78 cells treated for 48 h was (28.5±1.2)%, (31.3±0.8)%, (45.2±2.1)%, respectively ( F = 14.32, P < 0.05). When Hut-78 cells were treated with 1.0 μmol/L chidamide, 4.0 μmol/L arsenic trioxide or both of them (1.0 μmol/L chidamide+ 4.0 μmol/L arsenic trioxide) for 24 h, the relative expression level of bcl-2 protein was (58.4±2.9)%, (55.9±3.8)%, (53.2±2.1)%, respectively ( F = 17.52, P < 0.05); the relative expression level of VEGF protein was (60.5±4.2)%, (57.5±2.8)%, (50.9±3.5)%, respectively ( F = 7.36, P < 0.05). When Hut-78 cells were treated with 1.0 μmol/L chidamide, 4.0 μmol/L arsenic trioxide or both of them (1.0 μmol/L chidamide+ 4.0 μmol/L arsenic trioxide) for 48 h, the relative expression level of bcl-2 protein was (48.2±1.8)%, (40.1±2.2)%, (32.3±3.1)%, respectively ( F = 10.38, P < 0.05); the relative expression level of VEGF protein was (51.4±4.1)%, (48.9±2.9)%, (40.8±3.8)%, respectively ( F = 8.96, P < 0.05). When Hut-78 cells were treated with 1.5 μmol/L chidamide, 6.0 μmol/L arsenic trioxide or both of them (1.5 μmol/L chidamide+ 6.0 μmol/L arsenic trioxide) for 24 h, the relative expression level of bcl-2 protein was (55.4±3.1)%, (42.5±2.8)%, (37.8±4.2)%, respectively ( F= 10.35, P < 0.05); the relative expression level of VEGF protein was (49.2±3.4)%, (42.1±4.9)%, (34.3±5.1)%, respectively ( F= 17.82, P <0.05). When Hut-78 cells were treated with 1.5 μmol/L chidamide, 6.0 μmol/L arsenic trioxide or both of them (1.5 μmol/L chidamide+ 6.0 μmol/L arsenic trioxide) for 48 h, the relative expression level of bcl-2 protein was (40.1±0.9)%, (35.3±1.6)%, (27.8±2.4)%, respectively ( F = 15.36, P < 0.05); the relative expression level of VEGF protein was (40.3±3.8)%, (35.9±4.6)%, (20.1±2.9)%, respectively ( F = 9.78, P < 0.05). Conclusion:Chidamide and arsenic trioxide have synergistic inhibitory effects on T cell lymphoma Hut-78 cells, which may be related to the down-regulated expressions of bcl-2 and VEGR.