中文摘要：

目的探讨人核受体抑制剂Importazole（IPZ）对多发性骨髓瘤（MM）细胞周期、凋亡的影响及其可能的作用机制。方法用不同浓度IPZ处理骨髓瘤细胞系RPMI8226和NCI—H929细胞，用四甲基偶氮唑盐比色（MTT）法检测细胞活性，用流式细胞术测定细胞周期和细胞凋亡，westemblot法和凝胶迁移实验（EMsA）检测核内NF—KB的蛋白表达和DNA结合活性。结果IPz以时间浓度依赖方式抑制RPMI8226和NcI-H929细胞增殖及诱导凋亡，作用48h的半数抑制浓度（Ic50）分别为（4．43±0．41）、（4．78±0．35）μmoL／L。4μm0L／LIPZ分别作用RPMI8226和NcI—H929细胞48h，诱导S期细胞分别由（54．95±4．34）％、（51．38±2．43）％减少至（42．77±3．19）％、（40．98±6．46）％。以8、12、16μm0L／L的IPZ分别处理细胞48h，RPMI8226细胞凋亡率[（14．53±0．91）％、（32．57±1．80）％、（58．30±1．90）％]较空白对照组[（2．47±0．60）％]明显增加（P〈0．05），NCI—H929细胞凋亡率依次为（19．46±0．70）％、（46．02±1．10）％及（60．63±1．60）％，较空白对照组[（2．37±0．70）％]明显增加（P〈0．05）。8μmoL／LIPZ作用RPMI8226和NcI—H929细胞24h均能明显抑制NF—KB人核进而影响其与DNA的结合活性。结论IPZ通过阻断NF—KB信号通路抑制多发性骨髓瘤细胞增殖并诱导凋亡。

英文摘要：

Objective To investigate the effect of nuclear receptor inhibitor importazole （IPZ） on cell cycle and apoptosis of multiple myeloma （MM） cells and its regulatory mechanisms. Methods MM cell lines RPMI 8226 and NCI-H929 cells were treated with different concentrations of IPZ. Cell viability was detected through MTr method. Cell cycle and apoptosis were measured by flow cytometry （FCM）. Nuclear NF-K B protein expression was tested by Western blot. Electrophoretic mobility shift assay （EMSA） was used to analyze the DNA binding activity. Results IPZ induced a doseand timedependent inhibition of myeloma cells growth. And the ICso values of IPZ on RPMI 8226 and NCI-H929 after 48 hours incubation were （4.43 ± 0.41 ） and （4.78 ± 0.35 ） p,mol/L, respectively, and the percentages of S phase cells decreased from （54.95 ±4.34）% and（51.38 ±2.43）% to（42.77 ±3.19） % and （40.98 ± 6.46）%, respectively. After treatment with IPZ at 8 , 12 and 16 p, mo]/L, the apoptosis rate significantly increased from （2.47 ± 0.60 ） % of the control group to （ 14.53 ±0. 90） %, （ 32.57 ±1.80） % and （58.3± 1.9 ） % （ P 〈 0.05 ） in RPMI 8226 and from （2.37 ±0.70）% of the control group to （19.46± 0.70） % , （46.02± 1.10） % and （60.63 ± 1.60）% in NCI-H929, respectively. Treatment of RPMI 8226 and NCI-H929 cells with 8 μmol/L IPZ for 24 h could inhibit NF-K B import to nucleus and reduce its DNA binding activity. Conclusion The nuclear receptor inhibitor importazole inhibits proliferation and induces apoptosis of multiple myeloma cells by blocking the NF-K B signal pathway in vitro.