ABSTRACT
To explore the protective effects of 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3) on the bone marrow microenvironment in mice after irradiation and the underlying molecular mechanisms, a total of 150 7-wk-old male BALB/c mice were randomly divided into a normal group, an irradiation (IR) group and an irradiation+1,25-(OH)2D3 (IR+VD3) group. The mice in the IR+VD3 group were treated with 6.0 Gy 60Coγ rays, and 1,25-(OH)2D3 (dissolved in DMSO, 2.5 µg/kg) was administered once per day from 2 d before to 8 d after irradiation. Mice in the IR group were treated with the same dose of γ rays and an equal volume of DMSO. Subsequently, the body weights and the numbers of peripheral white blood cells (WBCs) were measured. Histological analysis of femur bone marrow was conducted to determine the proportion of adipose area as well. Finally, the expression of peroxisome proliferator-activated receptor-gamma (PPARγ) in bone marrow was detected by immunohistochemistry. After irradiation, the percentage of adipose area in the bone marrow was significantly increased, and the WBC number and body weight were markedly reduced. Compared with irradiation alone, the co-administration of 1,25-(OH)2D3 with irradiation markedly attenuated radiation-induced adipogenesis in bone marrow, resulted in fewer bone marrow stromal cells expressing PPARγ and enhanced the recovery of body weight and WBCs. These results indicate that 1,25-(OH)2D3 could accelerate the recovery of body weight and WBCs in irradiated mice and protect the bone marrow by inhibiting radiation-induced adipogenesis via the down-regulation of PPARγ expression.
Subject(s)
Adipogenesis/drug effects , Adipogenesis/radiation effects , Bone Marrow/drug effects , Bone Marrow/radiation effects , Gamma Rays/adverse effects , Vitamin D/analogs & derivatives , Adipocytes/drug effects , Adipocytes/radiation effects , Animals , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Gene Expression Regulation , Leukocyte Count , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/radiation effects , Male , Mice , Mice, Inbred BALB C , PPAR gamma/genetics , PPAR gamma/metabolism , Vitamin D/pharmacologyABSTRACT
OBJECTIVE: This study was aimed to investigate the effect of salinomycin combined with vincristine on the proliferation and apoptosis of Jurkat cells and its possible mechanisms. METHODS: The proliferation of Jurkat cells was examined by CKK-8 assay. Flow cytometry was used to assess cellular apoptosis. Levels of BCL-2, caspase-3, and caspase- 8 were measured by Western blot. RESULTS: The salinomycin or vincristine, either alone or in combination, inhibited the proliferation of Jurkat cells in a dose-dependent manner. Salinomycin combined with vincristine produced more obveous inhibition of cell proliferation than either compound used alone (P<0.05). Western blot analysis showed that the combined use of Sal and VCR reduced the expression of BCL-2 protein, and increased expression of caspase 3 and caspase 8 protein, more significantly. Furthermore, combination of Sal and VCR synergistally promoted apoptosis of the Jurkat cells (P<0.05). CONCLUSION: The combination of salinomycin and vincristine synergistically inhibits proliferation and promotes apoptosis of T-cell acute lymphoblastic leukemia Jurkat cells.
