,et al.Mechanism of radiosensitization effect of berberine on human nasopharyngeal carcinoma in hypoxia[J].Chinese Journal of Radiological Medicine and Protection,2014,34(9):663-667
Mechanism of radiosensitization effect of berberine on human nasopharyngeal carcinoma in hypoxia
Received:October 27, 2013  
DOI:10.3760/cma.j.issn.0254-5098.2014.09.005
KeyWords:Berberine  Nasopharyngeal carcinoma  Hypoxia  Radiosensitivity  Hypoxia induced factor
FundProject:江苏省2012年度普通高校研究生科研创新计划项目(CXZZ12_0588)
Author NameAffiliationE-mail
张弛 Department of Radiotherapy, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China  
张曲 Department of Radiotherapy, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China  
杨曦 Department of Radiotherapy, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China  
杨百霞 Department of Radiotherapy, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China  
秦嗪 Department of Radiotherapy, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China  
祝鸿程 Department of Radiotherapy, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China  
刘佳 Department of Radiotherapy, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China  
孙新臣 Department of Radiotherapy, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China sunxinchen2012@163.com 
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Abstract::
      Objective To investigate the radiosensitiation effect of berberine on human nasopharyngeal carcinoma (NPC) in hypoxia condition and explore the underlying mechanisms.Methods MTT assay, clonogenic assay and flow cytometry were performed to analyze cell proliferation, colony formation and apoptosis, respectively. Male nude mice inoculated subcutaneously with CNE-2 cells were used to examine the radiosensitization effect of berberine in vivo. The expressions of HIF-1α and VEGF were assessed by Western blot.Results Berberine efficiently inhibited the proliferation of CNE-2 cells in time-dependent and dose-dependent fashions with an IC50 of (14.9±2.2) μmol/L. Clonogenic survival assay showed that berberine (5 μmol/L) sensitized CNE-2 cells to ionizing radiation in hypoxia and its SERD0 was 1.27. Under hypoxic condition, berberine alone (5, 15 μmol/L) could induce apoptosis (t=5.01, 9.02,P<0.05) and it further promoted 8 Gy radiation-induced apoptosis (t=5.31, 9.91,P<0.05). Moreover, berberine significantly delayed the tumor growth in the combination group (berberine + irradiation) compared with the mice received irradiation alone or PBS (t=2.96, 14.52, P<0.05). Immunobloting assay showed that berberine inhibited the upregulation of HIF-1α and VEGF induced by hypoxia in CNE-2 cells.Conclusion Berberine confers radiosensitivity on hypoxic NPC in vitro and in vivo, which is probably associated with the downregulation of HIF-1α and VEGF expressions.
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