title: [Effect of valproic acid against angiogenesis of Kasumi-1 xenograft tumor in nude mice].
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.
authors.affiliation: Department of Hematology, Affiliated Hospital of Chengde Medical College, Chengde, Hebei Province, China.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Wang
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Cui-Min
authors.initials: CM
authors.lastname: Zhu
authors.forename: Li-Shuang
authors.initials: LS
authors.lastname: Zhao
authors.forename: Chang-Lai
authors.initials: CL
authors.lastname: Hao
mesh_terms: D042682:Angiopoietins / Q000378:metabolism; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014635:Valproic Acid / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D042682:Angiopoietins; D018952:Antigens, CD34; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D014635:Valproic Acid