title: SiRNA-mediated IGF-1R inhibition sensitizes human colon cancer SW480 cells to radiation.
abstract: OBJECTIVE
  Insulin like growth factor receptor 1 (IGF-1R) is well-documented to play a key role in radiation response and tumor radiosensitivity, thus offering an attractive clinic drug target to enhance tumor sensitivity to anti-cancer radiotherapy.
  
  
  METHODS
  Human colon carcinoma SW480 cells were transfected with the specific small interference RNA (siRNA) expression vector (pkD-shRNA-IGF-1R-V2) designed to target IGF-1R mRNA. The expression of IGF-1R mRNA and its protein among the transfected and untransfected cells were detected by semi-quantitative RT-PCR and ELISA assay. The changes in cell radiosensitivity were examined by MTT assay.
  
  
  RESULTS
  Transfection of mammalian expression vector pkD containing IGF-1R siRNA was shown to reduce IGF-1R mRNA levels by up to 95%. ELISA assay detected a similar inhibition of IGF-1R protein levels in cells transfected with IGF-1R siRNA. SW480 cells transfected with the expression vector for siRNA significantly rendered cells more sensitive to radiation and the highest radiation enhancement ratio was 2.02 +/- 0.08.
  
  
  CONCLUSIONS
  These data provide the first evidence that specific siRNA fragment (pkD-shRNA-IGF-1R-V2) targeting human IGF-1R mRNA is able to enhance colon cancer radiosensitivity. Also results indicated that, combining IGF-1R siRNA and radiation significantly enhances antitumor efficacy compared with either modality alone.
authors.affiliation: Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Kamal
authors.initials: K
authors.lastname: Yavari
authors.forename: Mohammad
authors.initials: M
authors.lastname: Taghikhani
authors.forename: Mohammad Ghannadi
authors.initials: MG
authors.lastname: Maragheh
authors.forename: Seyed A
authors.initials: SA
authors.lastname: Mesbah-Namin
authors.forename: Mohammad Hosein
authors.initials: MH
authors.lastname: Babaei
authors.forename: Ali Jabbary
authors.initials: AJ
authors.lastname: Arfaee
authors.forename: Hossein
authors.initials: H
authors.lastname: Madani
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Mirzaei
mesh_terms: D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000235:genetics*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011838:Radiation-Sensitizing Agents; D017526:Receptor, IGF Type 1