Affiliations: [a] First Department of Oncology Radiotherapy, Qingdao Central Hospital, Qingdao, Shandong, China | [b] Department of Oncology, Qingdao Third People’s Hospital, Qingdao, Shandong, China | [c] Second Department of Oncology Radiotherapy, Qingdao Central Hospital, Qingdao, Shandong, China | [d] Department of Oncology, MianYang Central Hospital, MianYang, Sichuan, China
Correspondence:
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Corresponding author: Rui Zong, First Department of Oncology %****␣cbm-32-cbm210016_temp.tex␣Line␣25␣**** Radiotherapy, Qingdao Central Hospital, Siliu Nan Road 127, 266042 Qindao, Shandong, China. E-mail: [email protected].
Abstract: PURPOSE: Insulin like growth factor receptor 1 (IGF-1R) has been documented to play a key role in radiation response, thereby offering an attractive drug target to enhance tumor sensitivity to radiotherapy. Here, we investigated wether knockdown of IGF-1R can sensitize colorectal cancer (CRC) cell lines to radiation. MATERIAL AND METHODS: Human colon carcinoma SW480 and HT-29 cells were transfected with specific small interference RNA (siRNA) to mediate IGF-1R depletion. The expression of IGF-1R mRNA and protein among transfected and untransfected cells was detected by Western blot analysis. Changes in cell proliferation and radiosensitivity were evaluated by the clonogenic survival assay. NVP-ADW742, an IGF-1R inhibitor, in combination with radiation was studied. RAD51, a measure for homologous recombination repair, and 53BP1, a maker for non-homologous end-joining (NHEJ), were determined by immunofluorescence for double-strand breaks (DSB) repair pathways. Cell cycle was also examined in the IGF-1R knockdown and IGF-1R-inhibited cells. RESULTS: CRC cell lines were selectively sensitized to radiation after siRNA-mediated IGF-1R depletion. NVP-ADW742 efficiently increases cancer cell response to radiation. Furthermore, initial formation of RAD51 foci after IR, and 53BP1 foci were significantly reduced in IGF-1R-depleted or with IGF-1R Inhibitor CRC cell lines. Lastly, IGF-1R-depleted or with IGF-1R Inhibitor caused more G2 phase cell arrest. CONCLUSION: Our findings demonstrate that depletion of IGF-1R lead to an increase in radiosensitivity in CRC.
