关键词: B细胞淋巴瘤, Jeko-1/R细胞, 组蛋白去乙酰化酶抑制剂, 西达本胺, 利妥昔单抗, CD20

Abstract: Objective To investigate the effect of histone deacetylase(HDAC)  inhibitor chidamide on the proliferation of rituximab-resistant B-cell lymphoma cells in vitro and its potential mechanism. Methods The proliferation inhibition rate of lymphoma Jeko-1 and Jeko-1/R cells was detected by CCK-8 method after treated with different concentrations of chidamide, rituximab or combination drugs. The expression of CD20 mRNA was detected by the RT-PCR, and the acetylation levels of histone H3 and H4 was detected by Western blot. Results 25 μg/mL, 50 μg/mL, 100 μg/mL and 200 μg/mL of rituximab could inhibit the proliferation of Jeko-1 cells in a dose-dependent manner at 48 h and the difference between the groups was statistically significant(F=38.533, P<0.001), and the proliferation inhibition rate was higher than that of Jeko-1/R cells (all P<0.001). 4 μmol/L, 8 μmol/L and 16 μmol/L of chidamide could inhibit the proliferation of Jeko-1 and Jeko-1/R cells in a dose-dependent manner at 48 h and the difference between the groups was statistically significant(F=17.968, P=0.003; F=51.456, P<0.001), whereas there was no statistically significant difference in the proliferation inhibition rate of Jeko-1 and Jeko-1/R cells exposed to chidamide with different concentrations (all P>0.05). When Jeko-1 cells and Jeko-1/R cells were treated by combining chidamide(8 μmol/L) with rituximab(100 μg/mL) for 48 h, their proliferation inhibition rates were higher than those treated by single-agent chidamide(P<0.001). Chidamide could up-regulate CD20 mRNA expression, histone H3 and H4 acetylation levels of Jeko-1/R cells in a dose-dependent manner at 48 h(P<0.001). Conclusion Chidamide can inhibit the proliferation of drug-resistant B-cell lymphoma Jeko-1/R cells, potentially up-regulating histone H3 and H4 acetylation levels and CD20 mRNA expression.

Key words: B-cell lymphoma, Jeko-1/R cells, Histone deacetylase inhibitor, Chidamide, Rituximab, CD20