IGF-1R depletion sensitizes colon cancer cell lines to radiotherapy

Purpose: Insulin-like growth factor receptor 1 (IGF-1R) has been identified as a key player in the radiation response, making it a promising drug target to enhance tumor sensitivity to radiotherapy. This study aimed to investigate whether knockdown of IGF-1R can sensitize colorectal cancer (CRC) cell lines to radiation.

Materials and Methods: Human colon carcinoma SW480 and HT-29 cells were transfected with small interference RNA (siRNA) to deplete IGF-1R. IGF-1R mRNA and protein expression levels in transfected and untransfected cells were measured by Western blot analysis. Changes in cell proliferation and radiosensitivity were assessed using the clonogenic survival assay. The effect of NVP-ADW742, an IGF-1R inhibitor, combined with radiation was also evaluated. RAD51, a marker for homologous recombination repair, and 53BP1, a marker for non-homologous end-joining (NHEJ), were analyzed by immunofluorescence to assess double-strand break (DSB) repair pathways. The cell cycle was examined in IGF-1R knockdown and IGF-1R-inhibited cells.

Results: IGF-1R depletion by siRNA selectively sensitized CRC cell lines to radiation. NVP-ADW742 also enhanced the cancer cells’ response to radiation. Moreover, the formation of RAD51 and 53BP1 foci after ionizing radiation (IR) was significantly reduced in IGF-1R-depleted or IGF-1R inhibitor-treated CRC cell lines. Additionally, IGF-1R depletion or inhibition led to an increased arrest of cells in the G2 phase.

Conclusion: Our findings demonstrate that IGF-1R depletion enhances radiosensitivity in CRC, suggesting that targeting IGF-1R could be a promising strategy to improve the efficacy of radiotherapy.