Dehydrogenase/reductase SDR family member 2 silencing sensitizes an oxaliplatin-resistant cell line to oxaliplatin by inhibiting excision repair cross-complementing group 1 protein expression

Oxaliplatin (Oxa)-based chemotherapy is widely used as the first-line treatment for colorectal cancer (CRC). However, Oxa-resistance is common for many postoperative CRC patients. To explore drug resistance in CRC, an Oxa-resistant cell line, HCT116/Oxa, was established from parental HCT116 cells. These Oxa-resistant cells exhibited characteristics of epithelial-mesenchymal transition (EMT) and a higher migratory capacity than parental cells. Protein profiles of HCT116/Oxa and HCT116 cells were compared using a tandem mass tag-based quantitative proteomics technique. The protein dehydrogenase/reductase SDR family member 2 (DHRS2) was revealed to be highly expressed in HCT116/Oxa cells. Silencing of DHRS2 in HCT116/Oxa cells effectively restored Oxa-sensitivity by suppressing the expression of excision repair cross-complementing group 1 protein via a p53-dependent pathway, and reversed the EMT phenotype. Overall, the suppression of DHRS2 expression may be a promising strategy for the prevention of Oxa-resistance in CRC.