التفاصيل البيبلوغرافية
| العنوان: |
Reduction of hypoxia-induced angiogenesis in ovarian cancer cells by inhibition of HIF-1 alpha gene expression. |
| المؤلفون: |
Bryant, Christopher1 csbryant@med.wayne.edu, Munkarah, Adnan2, Kumar, Sanjeev1, Batchu, Ramesh3, Shah, Jay1, Berman, Jeremy1, Morris, Robert1, Jiang, Zhong4, Saed, Ghassan4, Bryant, Christopher S5 (AUTHOR), Munkarah, Adnan R (AUTHOR), Batchu, Ramesh B (AUTHOR), Shah, Jay P (AUTHOR), Morris, Robert T (AUTHOR), Jiang, Zhong L (AUTHOR), Saed, Ghassan M (AUTHOR) |
| المصدر: |
Archives of Gynecology & Obstetrics. Dec2010, Vol. 282 Issue 6, p677-683. 7p. 2 Color Photographs, 2 Charts, 2 Graphs. |
| مصطلحات موضوعية: |
*GENE expression, *NEOVASCULARIZATION, *OVARIAN cancer, *CANCER cells, *HYPOXEMIA, *SMALL interfering RNA |
| مستخلص: |
Purpose: The goal of this study was to investigate the effects of silencing HIF-1 alpha gene expression with specific small interfering RNA (siRNA) on VEGF production and angiogenesis in epithelial ovarian cancer (EOC) cells. Methods: Two EOC cell lines, MDAH-2774 and SKOV-3, were cultured under normoxic (20% O(2)) and hypoxic (2% O(2)) conditions using standard techniques. After EOC cells were transfected with siRNA, HIF-1 alpha and VEGF mRNA levels were measured by real-time RT-PCR. Angiogenesis was evaluated utilizing an in vitro assay model consisting of human umbilical vein endothelial cells (HUVEC) and polymerized ECM Matrix. Results: Both EOC cell lines evaluated constitutively expressed HIF-1 alpha and VEGF mRNA. HIF-1 alpha and VEGF mRNA levels were significantly increased in response to hypoxia (P < 0.05). Under hypoxic conditions, inhibition of HIF-1 alpha gene expression by a specific siRNA resulted in a significant reduction in HIF-1 alpha and VEGF mRNA levels (P < 0.05). In the in vitro angiogenesis model, supernatant from the hypoxic EOC cells induced the HUVEC to form a complex tubular network, a hallmark of angiogenesis. Semi-quantitative analysis of the angiogenesis assay revealed a significant reduction in tube formation when supernatant from HIF-1 alpha siRNA-treated hypoxic EOC cell was used (P < 0.05). Conclusion: Inhibition of HIF-1 alpha expression by specific siRNA resulted in a significant decrease in VEGF production and angiogenesis. Further investigation of HIF-1 alpha inhibition for anti-tumor activity is warranted and may potentially prove HIF-1 alpha as a therapeutic target in the management ovarian cancer. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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