Inhibition of Notch and HIF enhances the antitumor effect of radiation in Notch expressing lung cancer
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- 作者：Yasuyuki Ikezawa ; Jun Sakakibara-Konishi…
- 关键词：Notch ; HIF ; 1 ; Hypoxia ; Radiosensitivity ; Lung cancer
- 刊名：International Journal of Clinical Oncology
- 出版年：2017
- 出版时间：February 2017
- 年：2017
- 卷：22
- 期：1
- 页码：59-69
- 全文大小：
- 刊物类别：Medicine
- 刊物主题：Oncology; Surgical Oncology; Cancer Research;
- 出版者：Springer Japan
- ISSN：1437-7772
- 卷排序：22
文摘
BackgroundThe Notch receptor plays an important role in various cell fate decisions during development and in cancer. We have previously reported that Notch3 is upregulated by radiation in non-small cell lung cancer (NSCLC) cell lines and that the Notch pathway inhibitor γ secretase inhibitor GSI (gamma-secretase inhibitor), when combined with radiation therapy, significantly suppressed the growth of lung cancer cells. However, little is known about the mechanism of Notch upregulation induced by radiation. Based on reports of Notch expression being activated through the hypoxia inducible factor 1 (HIF-1) under hypoxic conditions, we hypothesized that HIF-1 would be involved in radiation-induced Notch activation in NSCLC.