title: Sorafenib acts synergistically in combination with radiotherapy without causing intestinal damage in colorectal cancer.
abstract: OBJECTIVE
  Colorectal cancer is one of the commonest cancers. Chemoradiotherapy gives better results than radiotherapy or chemotherapy in colorectal cancer. To enhance radiosensitivity of tumor cells for chemoradiotherapy, targeted therapy drugs that act as radiosensitizers can be used. In the present study, we provide a scientific rationale for the clinical application of sorafenib as a radiosensitizer in colorectal cancer, without causing significant adverse effects on normal intestinal tissue.
  
  
  METHODS
  Three human colorectal adenocarcinoma cell lines (HCT116, HT-29, and SW480) were treated with sorafenib alone, or radiation followed by sorafenib. In vitro tests were performed using colony forming assays, cell cycle analysis, and comet assays. In addition, the effects of sorafenib and radiation therapy on the inhibition HT-29 tumor growth and survival of intestinal jejunum crypts were examined in vivo.
  
  
  RESULTS
  Sorafenib increased the radiosensitivity of tumor cells in human colon adenocarcinoma cell lines (HCT116, HT-29, and SW480), as well as in HT-29 xenograft animal models. Sorafenib, in combination with ionizing radiation, induced the accumulation of tumor cells in the G2-M phase and delayed the repair of DNA damage caused by ionizing radiation. The combination of sorafenib and ionizing radiation did not enhance the apoptosis of intestinal crypt cells, compared with the use of radiation alone.
  
  
  CONCLUSIONS
  We provide a scientific rationale for the use of sorafenib in combination with radiotherapy in colorectal cancer.
authors.affiliation: Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.
authors.forename: Youn Kyoung
authors.initials: YK
authors.lastname: Jeong
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Kim
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Eun Ho
authors.initials: EH
authors.lastname: Kim
authors.forename: Wonwoo
authors.initials: W
authors.lastname: Kim
authors.forename: Hunjoo
authors.initials: H
authors.lastname: Ha
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Jeong
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002588:Cesium Radioisotopes / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003106:Colon / Q000187:drug effects / Q000528:radiation effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D020552:Comet Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D018714:Radiotherapy, Adjuvant; D012007:Rectum / Q000187:drug effects / Q000528:radiation effects; D000077157:Sorafenib; D014183:Transplantation, Heterologous; D014410:Tumor Stem Cell Assay
chemical_list: D000970:Antineoplastic Agents; D002588:Cesium Radioisotopes; D010671:Phenylurea Compounds; D011838:Radiation-Sensitizing Agents; D009536:Niacinamide; D000077157:Sorafenib