Original ArticleSilencing peroxiredoxin-2 sensitizes human colorectal cancer cells to ionizing radiation and oxaliplatin

- Prx2 oxidation was associated with radiation response in colorectal cancer (CRC) cells.
- Radioresistant cells have higher monomer/dimer Prx2 ratio than radiosensitive cells.
- Prx2 inhibition sensitizes CRC cells to irradiation plus oxaliplatin in vitro.
- Prx2 inhibition sensitizes CRC cells to irradiation in vitro and in vivo.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. Antioxidant enzymes decrease the generation of ionizing radiation (IR)-induced free radicals and therefore are associate to radioresistance. The main goal of this work is to study the involvement of peroxiredoxin-2 (Prx2) in the radio and chemoradiotherapy response in CRC cells in vitro and in vivo. We found that Prx2 oxidation state is associated to differential response to ionizing radiation in CRC cell lines. HCT116 radioresistant CRC cell line have lower ROS levels and a higher monomer/dimer Prx2 ratio, compared to halfway resistant Caco-2 and T84, and radiosensitive LoVo cell line. Constitutive and transient Prx2 silencing in CRC cells increase ROS levels, and most importantly, enhance in vitro radiation sensitivity. In addition, we showed that administration of IR plus oxaliplatin in down regulated Prx2 HCT116 cells has higher citotoxic effect than in control cells. Finally, radiosensitizing effect of Prx2 depletion was confirmed in vivo. These results suggest that Prx2 is an important component in tumoral radiation response, and their inhibition could improve radio and chemoradiotherapy protocols in patients with CRC.