title: Combination effect of cetuximab with radiation in colorectal cancer cells.
abstract: OBJECTIVE
  Colorectal cancer (CRC) is one of the commonest malignant disorders and frequently associated with high expression of epidermal growth factor receptor (EGFR), resulting in advanced disease and a poor prognosis. In this study, we investigated the radiosensitizing effects of the selective EGFR inhibitor cetuximab in human CRC cell lines.
  
  
  METHODS
  Four human CRC cell lines, CaCo-2, HCT-8, LoVo, and WiDr, were treated with cetuximab and/or radiation. The effects on cell proliferation and viability were measured by MTT and annexin-V staining, and clonogenic survival assay. The in vivo effect on the growth of CRC xenografts was assessed in athymic nude mice.
  
  
  RESULTS
  Cetuximab in combination with radiation significantly inhibited the in vitro proliferation of CRC cells, with a concomitant increase in cell death, except in WiDr cells. Clonogenic survival assay confirmed that cetuximab worked as a radiosensitizer in three cetuximab-sensitivie CRC cells. However, no correlations were found between the radiosensitivity and EGFR expression level or mutation status of EGFR signaling molecules. In nude mice bearing CRC cell xenografts, cetuximab plus radiation significantly inhibited the tumor growth over either agent alone. Interestingly, the WiDr xenograft was also sensitive to cetuximab and/or radiation in vivo, suggesting host-mediated effects of cetuximab.
  
  
  CONCLUSIONS
  Cetuximab enhanced the radiosensitivity of CRC cells in vitro and efficiently inhibited xenograft tumor growth. This study provided a rationale for the clinical application of the selective EGFR inhibitor cetuximab in combination with radiation in CRC.
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul.
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Shin
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Kim
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: Lee
authors.forename: Seung-Sook
authors.initials: SS
authors.lastname: Lee
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Ji
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Jeong
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D000068818:Cetuximab; D017024:Chemotherapy, Adjuvant; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D018714:Radiotherapy, Adjuvant; D013997:Time Factors; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D014410:Tumor Stem Cell Assay; D018631:ras Proteins / Q000235:genetics
chemical_list: D017304:Annexin A5; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D011838:Radiation-Sensitizing Agents; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab