Effects of hypoxia inducible factor-2α on promoting angiogenesis of residual hepatocellular carcinoma after high-intensity focused ultrasound ablation / 中华肝脏病杂志
Chinese Journal of Hepatology
; (12): 112-117, 2015.
Article
in Chinese
| WPRIM (Western Pacific)
| ID: wpr-337029
Responsible library:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>
Full text:
Available
Database:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Immunohistochemistry
/
Blotting, Western
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Carcinoma, Hepatocellular
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Vascular Endothelial Growth Factor A
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Hypoxia-Inducible Factor 1, alpha Subunit
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Hep G2 Cells
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High-Intensity Focused Ultrasound Ablation
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Liver Neoplasms
/
Metabolism
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
Chinese
Journal:
Chinese Journal of Hepatology
Year:
2015
Document type:
Article