title: Melittin enhances radiosensitivity of hypoxic head and neck squamous cell carcinoma by suppressing HIF-1α.
abstract: 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.
authors: Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors: Xi
authors: X
authors: Yang
authors: Hongcheng
authors: H
authors: Zhu
authors: Yangyang
authors: Y
authors: Ge
authors: Jia
authors: J
authors: Liu
authors: Jing
authors: J
authors: Cai
authors: Qin
authors: Q
authors: Qin
authors: Liangliang
authors: L
authors: Zhan
authors: Chi
authors: C
authors: Zhang
authors: Liping
authors: L
authors: Xu
authors: Zheming
authors: Z
authors: Liu
authors: Yan
authors: Y
authors: Yang
authors: Yuehua
authors: Y
authors: Yang
authors: Jianxin
authors: J
authors: Ma
authors: Hongyan
authors: H
authors: Cheng
authors: Xinchen
authors: X
authors: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D008297:Male; D008555:Melitten / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D000077195:Squamous Cell Carcinoma of Head and Neck; D023041:Xenograft Model Antitumor Assays
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011838:Radiation-Sensitizing Agents; D008555:Melitten