ABSTRACT
Histone deacetylase 9 (HDAC9) belongs to the IIa subtype of HDACs. It is responsible for changing the structure of chromo-somes and regulating the transcription of genes by catalyzing the deacetylation of H3, H4, and non-histone proteins in vivo. Emerging studies have demonstrated that HDAC9 is closely related to tumors, but their expression and function in different tumors is not the same. This could ultimately lead to the opposite effect of promoting or suppressing tumorigenesis; unfortunately, the mechanisms are not clear. Recently, epigenetic treatment with HDAC deacetylases inhibitors (HDACIs) has become a hot topic and the development of selective HDACIs in combination with chemotherapy, radiotherapy, and immunotherapy has gained traction. However, studies target-ing HDAC9 are limited. This review summarizes the recent studies about HDAC9 in tumors.
ABSTRACT
OBJECTIVE@#To explore the protection and molecular mechanism of histone deacetylase inhibitors (HDACIs) on the spleen of rats with hemorrhagic shock.@*METHODS@#A total of 60 SPF male SD rats were selected for the modeling of severe hemorrhagic shock using the method of arterial and venous cannulation with the time-divided bleeding. The measurement of mean arterial blood pressure and blood lactic acid was used to verify the modeling. The modeled rats were randomly divided into shock group, shock + suberoylanilide hydroxamic acid (SAHA) group, shock + autogenous transfusion group and shock + SAHA + autogenous transfusion group. Three hours after the treatment, the spleen of rats was collected and TUNEL method was employed to detect the apoptosis of spleen cells in each group. The statistical analysis was performed. Afterwards, real-time PCR and western blot were employed to detect the expression of BCL-2, BAX and caspass3 in the spleen of rats in each group.@*RESULTS@#A total of 53 rats had successful modeling of severe hemorrhagic shock, with success rate of 88%. Cell apoptosis in the severe hemorrhagic model group was the most serious. After the intervention of HDACIs and the autogenous transfusion, the tissue injury was a bit recovered. Cell apoptosis was least in the shock + SAHA + autogenous transfusion group (P < 0.05). After the intervention of HDACIs and the autogenous transfusion, the relative expression of BCL-2 was significantly increased (P < 0.05), with highest relative expression of BCL-2 in shock + SAHA + autogenous transfusion group (P < 0.05). After the intervention of HDACIs and the autogenous transfusion, the relative expression of BAX was significantly decreased (P < 0.05), with lowest relative expression of BAX in the intervention group of single HDACIs. The change in the expression of caspass3 was similar to BAX, namely the relative expression of caspass3 was significantly decreased after the intervention of HDACIs and the autogenous transfusion (P < 0.05).@*CONCLUSIONS@#HDACIs and autogenous transfusion can all protect the spleen injury because of the severe hemorrhagic shock. Its molecular mechanism may be related to the regulation on the expression of BCL-2/BAX and caspass3, which may affect the apoptosis process of cells.
ABSTRACT
Objective To explore the protection and molecular mechanism of histone deacetylase inhibitors (HDACIs) on the spleen of rats with hemorrhagic shock. Methods A total of 60 SPF male SD rats were selected for the modeling of severe hemorrhagic shock using the method of arterial and venous cannulation with the time-divided bleeding. The measurement of mean arterial blood pressure and blood lactic acid was used to verify the modeling. The modeled rats were randomly divided into shock group, shock + suberoylanilide hydroxamic acid (SAHA) group, shock + autogenous transfusion group and shock + SAHA + autogenous transfusion group. Three hours after the treatment, the spleen of rats was collected and TUNEL method was employed to detect the apoptosis of spleen cells in each group. The statistical analysis was performed. Afterwards, real-time PCR and western blot were employed to detect the expression of BCL-2, BAX and caspass3 in the spleen of rats in each group. Results A total of 53 rats had successful modeling of severe hemorrhagic shock, with success rate of 88%. Cell apoptosis in the severe hemorrhagic model group was the most serious. After the intervention of HDACIs and the autogenous transfusion, the tissue injury was a bit recovered. Cell apoptosis was least in the shock + SAHA + autogenous transfusion group (P < 0.05). After the intervention of HDACIs and the autogenous transfusion, the relative expression of BCL-2 was significantly increased (P < 0.05), with highest relative expression of BCL-2 in shock + SAHA + autogenous transfusion group (P < 0.05). After the intervention of HDACIs and the autogenous transfusion, the relative expression of BAX was significantly decreased (P < 0.05), with lowest relative expression of BAX in the intervention group of single HDACIs. The change in the expression of caspass3 was similar to BAX, namely the relative expression of caspass3 was significantly decreased after the intervention of HDACIs and the autogenous transfusion (P < 0.05). Conclusions HDACIs and autogenous transfusion can all protect the spleen injury because of the severe hemorrhagic shock. Its molecular mechanism may be related to the regulation on the expression of BCL-2/BAX and caspass3, which may affect the apoptosis process of cells.
ABSTRACT
OBJECTIVE: Endometrial cancer is the most common malignant tumor of the female genital tract. Its incidence has increased in recent years, making up 13% of female genital cancers. Nevertheless, the search for agents effective in the treatment of either advanced or recurrent endometrial cancer has been disappointing. Histone deacetylase inhibitors (HDACIs) were recently found to be well-tolerated in patients with hematologic and solid malignancies. HDACIs have been shown to inhibit cancer cell proliferation, stimulate apoptosis, and induce cell cycle arrest. Our purpose was to investigate the antiproliferative effects of the HDACIs (sodium butyrate and HDAC-I1) against endometrial cancer cell line (Hec 1A) and normal endometrial cell line (T-HESCs). METHODS: MTS reduction assay was carried out to determine the cell viability. Cell cycle analysis and DNA fragmentation assay was done by fluorescent activated cell sorter analysis. The expression of cell cycle-regulatory and apoptosis-related proteins were evaluated by Western blot. Caspase 3 and 7 activity were measured by immuno-flouorescent staining. RESULTS: Each sodium butyrate and HDAC-I1 induced growth inhibition in a dose and time dependent manner in endometrial cancer cells but did not induce growth inhibition in normal endometrial cells. Treatment with each drugs in endometrial cancer cells increased the percentage of cells in subG1 phase. The expression of p53, p21, p27, FAS, and FAS legand were increased and it was associated with increased p21 and p27 expression in a p53-dependent manner. Activation of caspase-3, 7, 8, 9 and down-regulation of Bcl-2, up-regulation of Bax, with concomitant increase in PARP cleavage, were observed. CONCLUSION: These results demonstrate that sodium butyrate induced growth inhibition and apoptosis in human endometrial cancer cells rising their possibility applicable against human endometrial cancers.