SiRNA-mediated IGF-1R inhibition sensitizes human colon cancer SW480 cells to radiation.
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.
Yavari
Kamal
K
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Taghikhani
Mohammad
M
Maragheh
Mohammad Ghannadi
MG
Mesbah-Namin
Seyed A
SA
Babaei
Mohammad Hosein
MH
Arfaee
Ali Jabbary
AJ
Madani
Hossein
H
Mirzaei
Hamid Reza
HR
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
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011838:Radiation-Sensitizing Agents; D017526:Receptor, IGF Type 1