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Objective To observe the effect of panobinostat (LBH589) on the early brain injury (EBI) in the model of subarachnoid hemorrhage(SAH) in SD rats.Methods SD rats were randomly divided into 4 groups:sham(10 rats) and SAH(10 rats),SAH + vehicle(20 rats) and SAH + Panobinostat (20 rats).Drug or vehicle was given by lateral-ventricular stereotaxic injection 24h before the SAH model was introduced.Water contents and the neurological scores were determined at 24h post-SAH.The levels of Ac-H3K27 in frontal and lateral lobe were detected by Western blot.Results The mean neurological score of the SAH group was higher than that of the sham group(F =13.000,P =0.007).The water content of the SAH group was higher than that of the sham group (F =8.229,P =0.019).The level of Ac-H3K27 was higher in the SAH + Panobinostat group than that in the SAH +vehicle group(F =41.250,P =0.000).The mean neurological score of the SAH + Panobinostat group was lower than that of the SAH + vehicle group(F =9.560,P =0.011).The water content of the SAH + Panobinostat group was lower than that of the SAH + vehicle group (F =8.211,P =0.020).The correlation analysis indicated that the level of acetylation of H3 was negatively correlated with the neurological score (r =-0.585,P =0.046).Conclusion Panobinostat can improve the neurological behavior and alleviate early brain injury in the SAH model.
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Objective@#To observe the effect of panobinostat (LBH589) on the early brain injury (EBI) in the model of subarachnoid hemorrhage(SAH) in SD rats.@*Methods@#SD rats were randomly divided into 4 groups: sham(10 rats) and SAH(10 rats), SAH+ vehicle(20 rats) and SAH+ Panobinostat(20 rats). Drug or vehicle was given by lateral-ventricular stereotaxic injection 24h before the SAH model was introduced.Water contents and the neurological scores were determined at 24h post-SAH.The levels of Ac-H3K27 in frontal and lateral lobe were detected by Western blot.@*Results@#The mean neurological score of the SAH group was higher than that of the sham group(F=13.000, P=0.007). The water content of the SAH group was higher than that of the sham group (F=8.229, P=0.019). The level of Ac-H3K27 was higher in the SAH+ Panobinostat group than that in the SAH+ vehicle group(F=41.250, P=0.000). The mean neurological score of the SAH+ Panobinostat group was lower than that of the SAH+ vehicle group(F=9.560, P=0.011). The water content of the SAH+ Panobinostat group was lower than that of the SAH+ vehicle group(F=8.211, P=0.020). The correlation analysis indicated that the level of acetylation of H3 was negatively correlated with the neurological score(r=-0.585, P=0.046).@*Conclusion@#Panobinostat can improve the neurological behavior and alleviate early brain injury in the SAH model.
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Objective To study the effect of new generation histone deacetylase inhibitor LBH589 single-drug or combined with the mouse serum which contains the radix echinopsis on multiple myeloma (MM) cell line U266 and their mechanism.Methods The acetylation level of α-tublin which was a substrate of HDAC6 was detected by Western blot.The chemical force between Heat shock protein 90 (HSP90) and its client proteins was detected by immune precipitation (IP).Results The different concentrations of LBH589 single drug (0,20,50 nmol/L),and 50 nmol/L combined with the mouse serum which contained the radix echinopsis (1 g/ml) were able to inhibit the proliferation of U266 cell.With the increase of drug concentration and the extension of time,the acetylation levels of α-tublin and HSP90 increased gradually (at 24 or 48 hours) in a dose dependent (P ＜ 0.05).The inhibition of LBH589 combined with the mouse serum was stronger than that of LBH589 single drug (P ＜ 0.05).Conclusion LBH589 could inhibit the growth of MM cells and their cell cycles,and induce the apoptosis of MM cell line U266.
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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.