title: Bortezomib enhances the radiosensitivity of hypoxic cervical cancer cells by inhibiting HIF-1α expression.
abstract: OBJECTIVE
  This study aimed to investigate the radiosensitivity of bortezomib to cervical cancer and the possible underlying mechanism.
  
  
  METHODS
  HeLa and SiHa cell lines with or without hypoxia treatment were divided into control, radiation alone, bortezomib alone, and radiotherapy plus bortezomib groups. CCK8 assay, clone formation assay, flow cytometry, and immunofluorescence test were used to measure cell proliferation, colony formation, apoptosis, and DNA double-strand break (DSB). Western blot analysis was performed to detect the expression of HIF-1α, PARP-1, and caspase-3, -8, and -9.
  
  
  RESULTS
  Statistical analysis of data revealed that bortezomib at nanomolar level exerted a radiosensitization effect on both cervical cancer cell lines in normoxia or hypoxia. Western blot analysis showed that the drug could inhibit hypoxia-related HIF-1α expression to increase apoptosis-related caspase-3, -8, and -9 activation and DNA DSB-related PARP-1 cleavage.
  
  
  CONCLUSIONS
  Radiotherapy sensitization of bortezomib on cervical cancer cell lines had a drug-dose relation, and sensitization in hypoxia was more remarkable than in normoxia. Bortezomib may be a potential radiotherapy sensitization drug for cervical cancer.
authors.affiliation: Department of Radiotherapy, The Second People's Hospital of Lianyungang, Lianyungang Hospital Affiliated to Bengbu Medical College China.
authors.forename: Heqing
authors.initials: H
authors.lastname: Cui
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Qin
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University China.
authors.forename: Zheming
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Radiotherapy, The Second People's Hospital of Lianyungang, Lianyungang Hospital Affiliated to Bengbu Medical College China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Radiotherapy, The Second People's Hospital of Lianyungang, Lianyungang Hospital Affiliated to Bengbu Medical College China.
authors.forename: Hongcheng
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Radiotherapy, The Second People's Hospital of Lianyungang, Lianyungang Hospital Affiliated to Bengbu Medical College China.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Radiotherapy, The Second People's Hospital of Lianyungang, Lianyungang Hospital Affiliated to Bengbu Medical College China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Meng
authors.affiliation: Department of Radiotherapy, The Second People's Hospital of Lianyungang, Lianyungang Hospital Affiliated to Bengbu Medical College China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Radiotherapy, The Second People's Hospital of Lianyungang, Lianyungang Hospital Affiliated to Bengbu Medical College China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Radiotherapy, The Second People's Hospital of Lianyungang, Lianyungang Hospital Affiliated to Bengbu Medical College China.
authors.forename: Guanhong
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Radiotherapy, Nantong Tumor Hospital Affiliated to Nantong University China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University China.
authors.forename: Xinchen
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Radiotherapy, The Second People's Hospital of Lianyungang, Lianyungang Hospital Affiliated to Bengbu Medical College China.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D000069286:Bortezomib / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011838:Radiation-Sensitizing Agents; D000069286:Bortezomib; D053148:Caspase 3
keywords: Bortezomib; HIF-1α; cervical cancer; hypoxia; radiosensitivity