PURPOSE: 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. MATERIAL AND 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. CONCLUSION: 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.
PURPOSE: 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. MATERIAL AND METHODS:Humancolon 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. CONCLUSION: These data provide the first evidence that specific siRNA fragment (pkD-shRNA-IGF-1R-V2) targeting humanIGF-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: Melanie Spitzner; Georg Emons; Frank Kramer; Jochen Gaedcke; Margret Rave-Fränk; Jens-Gerd Scharf; Peter Burfeind; Heinz Becker; Tim Beissbarth; B Michael Ghadimi; Thomas Ried; Marian Grade Journal: Int J Radiat Oncol Biol Phys Date: 2010-11-15 Impact factor: 7.038
Authors: Almudena Valenciano; Luis Alberto Henríquez-Hernández; Mercedes Moreno; Marta Lloret; Pedro Carlos Lara Journal: Transl Oncol Date: 2012-02-01 Impact factor: 4.243
Authors: A R M Ruhul Amin; Phillip A Karpowicz; Thomas E Carey; Jack Arbiser; Rita Nahta; Zhuo G Chen; Jin-Tang Dong; Omer Kucuk; Gazala N Khan; Gloria S Huang; Shijun Mi; Ho-Young Lee; Joerg Reichrath; Kanya Honoki; Alexandros G Georgakilas; Amedeo Amedei; Amr Amin; Bill Helferich; Chandra S Boosani; Maria Rosa Ciriolo; Sophie Chen; Sulma I Mohammed; Asfar S Azmi; W Nicol Keith; Dipita Bhakta; Dorota Halicka; Elena Niccolai; Hiromasa Fujii; Katia Aquilano; S Salman Ashraf; Somaira Nowsheen; Xujuan Yang; Alan Bilsland; Dong M Shin Journal: Semin Cancer Biol Date: 2015-03-06 Impact factor: 15.707