[Effects of hypoxia inducible factor-2α on promoting angiogenesis of residual hepatocellular carcinoma after high-intensity focused ultrasound ablation].
Zhonghua Gan Zang Bing Za Zhi
; 23(2): 112-7, 2015 Feb.
Article
em Zh
| MEDLINE
| ID: mdl-25880977
ABSTRACT
OBJECTIVE:
To investigate the dynamic features of angiogenesis in residual tumors after high intensity focused ultrasound (HIFU),and to determine the temporal effect and mechanism of hypoxia inducible factor-2 alpha (HIF-2a) in the angiogenic process of residual tumors.METHODS:
Xenograft tumors of HepG2 cells were generated by subcutaneously inoculating athymic BALB/c nu/nu mice with the hepatoma cells.About 30 days after inoculation,all mice (except in the control group) were treated by HIFU and assigned randomly to the following 7 groups according to various time intervals post-treatment1st,3rd,5th day and 1st,2nd,3rd,4th week when the residual tumor tissues were obtained from the experimental groups.Protein levels of HIF-2a and vascular growth factor A (VEGF-A) were quantified by immunohistochemistry and western blotting,and mRNA levels were measured by (real-time quantitative) qPCR. Microvascular density (MVD) was calculated by counting the CD31-positive vascular endothelial cells identified by means of an immunohistochemical staining method.RESULTS:
Compared with results from the control group,the protein and mRNA levels of HIF-2a expression reached the highest level in the experimental mice at the 2nd week (P=0.000 and P < 0.01 respectively),and were decreased thereafter(3rd week and 4th week, P=0.000 and P < 0.05).VEGF-A expression in the residual tumor tissues group that received HIFU was significantly decreased,compared with the control group,at all time points uPto 1 week (all P=0.000 and P < 0.01),but the levels increased compared to controls in the 2nd through 4th week (all P=0.000, P < 0.05). Similar results were obtained for MVD.CONCLUSION:
HIFU treatment can inhibit angiogenesis in residual hepatoma tissues in the short-term (1 to 2 weeks post-treatment) in mice with hepatocellular carcinoma,but can promote angiogenesis overtime (2 to 4 weeks post-treatment); the angiogenic process may involve the HIF-2α/VEGFA pathway.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
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Subunidade alfa do Fator 1 Induzível por Hipóxia
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Ablação por Ultrassom Focalizado de Alta Intensidade
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Neoplasias Hepáticas
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Neovascularização Patológica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
Zh
Ano de publicação:
2015
Tipo de documento:
Article