槲皮素联合硼替佐米或雷利度胺对抑制HL-60细胞增殖的影响

Effects of quercetin in combination with bortezomib or lenalidomide on inhibition of proliferation of HL-60 cells

目的:前期研究证实槲皮素可有效抑制白血病细胞株HL-60细胞增殖,本研究旨在进一步筛选与槲皮素有协同抗白血病作用的药物。方法:不同浓度硼替佐米与HL-60细胞孵育48 h,槲皮素联合硼替佐米孵育HL-60细胞48 h。不同浓度雷利度胺与HL-60细胞孵育48 h,槲皮素联合雷利度胺孵育HL-60细胞48 h。CCK-8法检测细胞存活率。结果:硼替佐米可显著抑制HL-60细胞的增殖。槲皮素联合硼替佐米的IC50值是49.24μmol/L,比单用槲皮素下降13.44μmol/L;等辐射分析法显示两药有协同作用。低浓度雷利度胺(5、10、20、40、80μmol/L)的细胞存活率与对照组比较无统计学差异,高浓度雷利度胺(160、320μmol/L)细胞存活率显著降低;雷利度胺联合槲皮素的IC50值较单用槲皮素无明显下降;等辐射分析法显示两药无协同作用。结论:硼替佐米可显著抑制HL-60细胞的增殖,槲皮素与硼替佐米有协同抑制HL-60细胞增殖的作用。雷利度胺抑制HL-60细胞增殖作用较弱,与槲皮素在抑制HL-60细胞增殖方面无协同作用。

Objective Our preliminary study demonstrates that quercetin can inhibit the proliferation of HL-60 cells. This sudy aimed to find some drugs which could have synergistic effects with quercetin on apoptosis of HL-60 cells. Methods HL-60 cells were cultured with bortezomib at different concentrations （1, 2, 4, 8, 16, and 32μmol/L） alone or combined with quercetin at different concentrations for 48 h. HL-60 cells were cultured with lenalidomide at different concentrations （5, 10, 20, 40, 80, 160, and 320 μmol/L） alone or in combination with quercetin at different concentrations for 48 h. The CCK-8 assay was used to determine the effects on proliferation of HL-60 cells. Results Bortezomib significantly inhibited the proliferation of HL-60 cells （P〈0.01）. IC50 of quercetin was 49.24μmol/L after cells treated by quercetin combined with bortezomib, which was 13.44μmol/L lower than that treated by quercetin alone. Isobolographic analysis revealed the two drugs had synergistic effect. The results of cell viability of HL-60 cells treated by lenalidomide at lower concentrations （5, 10, 20, 40, and 80μmol/L）were not different from those of the control group （P 〉 0.05）. The results of cell viability of HL-60 cells treated by lenalidomide at higher concentrations （160 and 320μmol/L） were lower than those of the control group （P〈0.05）. IC50 of quercetin after cells treated by quercetin combined with bortezomib was not different from that treated by quercetin alone. Isobolographic analysis revealed the two drugs had no synergistic effect. Conclusions Bortezomib can inhibit the proliferation of HL-60 cells and it has a synergistic effect with quercetin on HL-60 cells. Lenalidomide has a weaker role in inhibition of the proliferation of HL-60 cells, and it has no synergistic effect with quercetin on HL-60 cells.