Melittin enhances radiosensitivity of hypoxic head and neck squamous cell carcinoma by suppressing HIF-1α
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- 作者：Xi Yang (1)
Hongcheng Zhu (1)
Yangyang Ge (2)
Jia Liu (1)
Jing Cai (2)
Qin Qin (1)
Liangliang Zhan (1)
Chi Zhang (1)
Liping Xu (1)
Zheming Liu (1)
Yan Yang (1)
Yuehua Yang (1)
Jianxin Ma (3)
Hongyan Cheng (4)
Xinchen Sun (1) - 关键词：Melittin ; Head and neck squamous cell carcinoma ; Hypoxia ; Radiosensitivity ; HIF ; 1α
- 刊名：Tumor Biology
- 出版年：2014
- 出版时间：October 2014
- 年：2014
- 卷：35
- 期：10
- 页码：10443-10448
- 全文大小：561 KB
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Hongcheng Zhu (1)
Yangyang Ge (2)
Jia Liu (1)
Jing Cai (2)
Qin Qin (1)
Liangliang Zhan (1)
Chi Zhang (1)
Liping Xu (1)
Zheming Liu (1)
Yan Yang (1)
Yuehua Yang (1)
Jianxin Ma (3)
Hongyan Cheng (4)
Xinchen Sun (1)
1. Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China
2. Department of Radiation Oncology, The Affiliated Tumor Hospital of Nantong University, Nantong, China
3. Department of Radiation Oncology, The Second People’s Hospital of LianYungang, Lianyungang Hospital Affiliated to Bengbu Medical College, Lian Yungang, China
4. Department of General Internal Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China - ISSN：1423-0380
文摘
Hypoxia is a widespread phenomenon present in many human solid tumors and is associated with a poor prognosis and therapy resistance. Here, we tested the feasibility of melittin, a major component of bee venom, on radiosensitization of hypoxic head and neck squamous cell carcinoma (HNSCC). CNE-2 and KB cells were treated with melittin and radiation response was determined. Cell viability, cytotoxicity and apoptosis induction were examined by CCK-8 assay, colony formation assay, and flow cytometry. Expression of hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF) proteins were assessed using western blotting. Additionally, we also examined the effect of melittin on tumor growth and radiosensitivity in vivo using a xenograft model of HNSCC. Treatment with melittin resulted in cell growth inhibition, induction of cell apoptosis, and reduction of HIF-1α and VEGF expression, which has been linked to hypoxia cell radioresistance. In addition, intraperitoneal injection of melittin significantly reduced the growth of HNSCC tumors in CNE-2 tumor-bearing mice. These data suggest that melittin enhances radiosensitivity of HNSCC under hypoxia condition, and this is associated with the suppression of HIF-1α expression. Melittin appears to be a potential radiotherapy sensitization agent due to its significant antihypoxia activity.