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

脱氢酶/还原酶 SDR 家族成员 2 沉默通过抑制切除修复交叉互补组 1 蛋白表达使奥沙利铂耐药细胞系对奥沙利铂敏感

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作者:Ji-Min Li, Guan-Min Jiang, Liang Zhao, Fang Yang, Wei-Qi Yuan, Hao Wang, Yi-Qin Luo

Abstract

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.

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