Hypoxia inducible factor‐1α/vascular endothelial growth factor signaling activation correlates with response to radiotherapy and its inhibition reduces hypoxia‐induced angiogenesis in lung cancer. Issue 9 (15th June 2018)

• Record Type: Journal Article
• Authors: Zhu, Hongjun; Zhang, Shuanglin
• Is Part Of: Journal of cellular biochemistry. Volume 119:Issue 9(2018)
• Page Start: 7707
• Page End: 7718
• Publication Date: 2018-06-15
• Subjects: angiogenesis -- hypoxia‐inducible factor 1α/vascular endothelial growth factor (HIF‐1α/VEGF) pathway -- hypoxia -- lung cancer -- resistance to radiotherapy; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.27120
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Like other tumors, lung cancer must induce angiogenesis as it grows. Hypoxia‐inducible factor 1α (HIF‐1α) is the inducible subunit of the HIF‐1 transcription factor that regulates genes involved in the response to hypoxia, some of which contributes to angiogenesis. Vascular endothelial growth factor (VEGF) is one of the genes upregulated by HIF‐1 and is the primary cytokine in relation to angiogenesis. In this study we tested whether aberrant activation of hypoxia inducible factor‐1α/vascular endothelial growth factor (HIF‐1α/VEGF) pathway correlates with response to radiotherapy and examined the response of lung cancer cells to hypoxia in vitro. We determined increased expressions of HIF‐1α and VEGF‐A in 76 cancerous tissues of responders (complete remission and partial remission). HIF‐1α and VEGF‐A were shown to be upregulated in lung cancer cells in response to hypoxia. The treatment with anti‐HIF‐1α siRNA prior to hypoxia exposure was shown to decrease HIF‐1α and VEGF‐A expressions and reduce hypoxia‐induced angiogenesis, suggesting that HIF‐1α expression resulted in increased VEGF‐A expression and activation of HIF‐1α/VEGF pathway was responsible for hypoxia‐induced angiogenesis. In conclusion, we identified the relationship between HIF‐1α/VEGF pathway and response to radiotherapy and its role in angiogenesis in lung cancer in vitro. HIF‐1α/VEGF pathway as a target for antiangiogenic treatment strategies for this tumor requires further investigation. Abstract : Hypoxia can promote cell growth and inhibit cell apoptosis by activating the hypoxia‐inducible factor 1α/vascular endothelial growth factor pathway in the tumor microenvironment, thereby promoting the resistance to radiotherapy and angiogenesis in lung cancer.