Effect of nuclear receptor inhibitor importazole on the proliferation and apoptosis of multiple myeloma cells / 中华血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of nuclear receptor inhibitor importazole (IPZ) on cell cycle and apoptosis of multiple myeloma (MM) cells and its regulatory mechanisms.</p><p><b>METHODS</b>MM cell lines RPMI 8226 and NCI-H929 cells were treated with different concentrations of IPZ. Cell viability was detected through MTT method. Cell cycle and apoptosis were measured by flow cytometry (FCM). Nuclear NF-κBprotein expression was tested by Western blot. Electrophoretic mobility shift assay (EMSA) was used to analyze the DNA binding activity.</p><p><b>RESULTS</b>IPZ induced a dose- and time- dependent inhibition of myeloma cells growth. And the IC50 values of IPZ on RPMI 8226 and NCI-H929 after 48 hours incubation were (4.43±0.41) and (4.78±0.35) μmol/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 μmol/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-κB import to nucleus and reduce its DNA binding activity.</p><p><b>CONCLUSION</b>The nuclear receptor inhibitor importazole inhibits proliferation and induces apoptosis of multiple myeloma cells by blocking the NF-κB signal pathway in vitro.</p>