Study on histone deacetylase inhibitor LBH589 reversal of multiple myeloma cells’ drug resistance mechanism in vitro / 白血病·淋巴瘤

ABSTRACT

Objective To study on a new generation of histone deacetylase inhibitor LBH589 on multiple myeloma (MM) resistant cells associated with changes in gene expression,and the mechanism of LBH589 reversal of MM cells' drug resistance.Methods By Western blot analysis,LBH589 (0,20,50 nmol/L) and 50 nmol/L LBH589 combined respectively with dexamethasone of 5 μmol/L at 24 h,expression of histone H4 acetylation and bcl-X gene on MMIR cells were detected.By real-time fluorescence quantitative PCR analysis,LBH589 (0,20,50 nmol/L) and 50 nmol/L LBH589 combined respectively with dexamethasone of 5 μmol/L at 24 h and 48 h,expression of TOSO on MM1R cells were detected.Results Western blot analysis showed that single LBH589 and combined with dexamethasone showed at 24 h the up-regulation on expression of the histone H4 acetylation[(0.205±0.008) ％,(0.346±0.009) ％,(0.580±0.053) ％,(0.986±0.012) ％,F =992.957,P =0.032],while down-regulation on expression of the bcl-X in MM1R cells in a dose-dependent manner[(1.210±0.160) ％,(0.930±0.036) ％,(0.730±0.017) ％,(0.488±0.029) ％,F =56.432,P =0.028].However,the group of single LBH589 was less effective than the combined group (all P ＜ 0.05).Real-time fluorescence quantitative PCR analysis showed single LBH589 and that combined with dexamethasone showed at 24 h and 48 h,the down-regulation on expression of the TOSO in MM1R cells in a dose-dependent manner,24 h specific numerical were (1.00±0.00) ％,(0.55±0.01) ％,(0.47±0.01) ％,(0.38±0.01) ％ (F =1006.344,P =0.041),48 h specific numerical were (1.00±0.00) ％,(0.39±0.04) ％,(0.05±0.01) ％,(0.03±0.00) ％ (F =2383.977,P =0.045),however,the group of single LBH589 was less effective than the combined group (all P ＜ 0.05).Conclusion Histone deacetylase inhibitor LBH589 can recover dexamethasone sensitivity of MM1R through effect the gene expression of bcl-X and TOSO,promot histone acetylation,and inducing cell apoptosis to treat tumor.