Effect of valproic acid against angiogenesis of Kasumi-1 xenograft tumor in nude mice.
10.7534/j.issn.1009-2137.2013.01.016
- Author:
Li-Hong WANG
1
;
Zhi-Hua ZHANG
;
Lei ZHAO
;
Cui-Min ZHU
;
Li-Shuang ZHAO
;
Chang-Lai HAO
Author Information
1. Department of Hematology, Affiliated Hospital of Chengde Medical College, Chengde, Hebei Province, China.
- Publication Type:Journal Article
- MeSH:
Angiopoietins;
metabolism;
Animals;
Antigens, CD34;
metabolism;
Cell Line, Tumor;
Female;
Humans;
Leukemia, Myeloid, Acute;
metabolism;
pathology;
Mice;
Mice, Inbred BALB C;
Mice, Nude;
Neovascularization, Pathologic;
metabolism;
RNA, Messenger;
genetics;
Valproic Acid;
pharmacology;
Vascular Endothelial Growth Factor A;
metabolism;
Xenograft Model Antitumor Assays
- From:
Journal of Experimental Hematology
2013;21(1):73-77
- CountryChina
- Language:Chinese
-
Abstract:
This study was aimed to investigate the effect of valproic acid (VPA), a histone deacetylase inhibitor, on angiogenesis of acute myeloid leukemia in vivo and vitro, and to explore its molecular mechanism. Human t (8;21) AML cell line Kasumi-1 cells were treated with VPA at different concentration for 3 d, the mRNA and protein expression levels of Ang1 and Ang2 were determined by semi-quantitative RT-PCR and Western blot respectively. Nude mice model with xenograft Kasumi-1 tumor was established by subcutaneous inoculation of Kasumi-1 cells. The CD34, Ang1 and Ang2 protein levels were analyzed by immunohistochemistry method. The mRNA and protein expression levels of Ang1, Ang2 and VEGF were determined by semi-quantitative RT-PCR and Western blot. The results showed that in vitro, VPA at 3 mmol/L downregulated the Ang mRNA relative expression level for Ang1 from 0.360 ± 0.116 to 0.040 ± 0.008, Ang2 from 0.540 ± 0.049 to 0.146 ± 0.038. The animal experiment further verified that VPA 500 mg/kg, ip, for 14 d, reduced the relative expression of Ang1, Ang2 and VEGF mRNA and proteins in Kasumi-1 tumor of nude mice, and reduced microvascular density in xenograft tumor of nude mice (8.470 ± 0.300 vs 2.600 ± 0.200). It is concluded that VPA significantly inhibits tumor angiogenesis through the regulation of angiopoietins, thereby inhibits the proliferation and metastasis of leukemia cells.
