title: Reverse resistance to radiation in KYSE-150R esophageal carcinoma cell after epidermal growth factor receptor signal pathway inhibition by cetuximab.
abstract: OBJECTIVE
  The purpose of our study is to examine the capacity of cetuximab to reverse radiation resistance and investigate molecular mechanisms in human radiation-resistant esophageal carcinoma cell line KYSE-150R.
  
  
  METHODS
  The radioresistant cell line KYSE-150R was established by using fractionated irradiation (FIR). The KYSE-150R cell line was exposed to radiation, treatment with cetuximab, and combined treatment. Cell cycle distribution and apoptosis were analyzed using flow cytometry. Radiation survival was analyzed using clonogenic assays. RT(2) profiler PCR array was performed to analyze EGF/PDGF signaling pathway genes.
  
  
  RESULTS
  The established esophageal carcinoma cell line KYSE-150R showed higher radioresistance than parental cell line. Cetuximab could reverse the radiation resistance of KYSE-150R cells. Cell cycle analysis showed that combination with radiation and cetuximab resulted in the accumulation of cells in G1 and G2/M phases, with the reduction of cells within the S phase. Cetuximab enhanced the apoptosis induced by radiation. RT(2) profiler array showed that some intracellular signaling genes deriving from EGF/PDGF signaling pathway regulated by cetuximab.
  
  
  CONCLUSIONS
  Irradiation combined with EGFR blocked by cetuximab may reverse the resistance to radiation in radioresistant esophageal carcinoma cell. The mechanisms may include cell cycle perturbation and enhancement of radiation-induced apoptosis. Further studies are needed to evaluate the role of cetuximab in combination with radiotherapy in the management of esophageal carcinoma.
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Wenzhou Medical College, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Jing
authors.forename: Ling
authors.initials: L
authors.lastname: Gong
authors.forename: Cong-Ying
authors.initials: CY
authors.lastname: Xie
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Hua-Fang
authors.initials: HF
authors.lastname: Su
authors.forename: Xia
authors.initials: X
authors.lastname: Deng
authors.forename: Shi-Xiu
authors.initials: SX
authors.lastname: Wu
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D000068818:Cetuximab; D066246:ErbB Receptors / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D015870:Gene Expression; D006801:Humans; D011836:Radiation Tolerance / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000068818:Cetuximab