Oxaliplatin induces ferroptosis and oxidative stress in HT29 colorectal cancer cells by inhibiting the Nrf2 signaling pathway

Oxaliplatin is a third-generation platinum drug that is used as first-line chemotherapy for colorectal cancer (CRC). Ferroptosis has been demonstrated to induce cell death and oxidative stress in CRC. The aim of the present study was to investigate whether oxaliplatin could exert anticancer effects on CRC by promoting ferroptosis and oxidative stress. Cell viability and apoptosis were assessed by performing Cell Counting Kit-8 and TUNEL assays, respectively, in the presence or absence of the ferroptosis inducer, erastin. Western blotting was performed to detect the levels of certain nuclear factor erythroid 2-related factor 2 (Nrf2)-associated proteins in HT29 cells treated with oxaliplatin. Furthermore, after treating cells with the Nrf2 activator, NK-252, Fe²⁺ was detected in cells using a commercial kit. Ferroptosis-associated protein expression was also evaluated via western blotting. Additionally, ELISA was adopted to measure the levels of oxidative stress-related factors. Following the addition of erastin, iron ion content, ferroptosis-related protein expression and the levels of oxidative stress-related factors were assayed as described previously. The results of the present study demonstrated that oxaliplatin inhibited viability and the Nrf2 signaling pathway in CRC cells. In addition, oxaliplatin promoted ferroptosis and oxidative stress in CRC cells by inhibiting the Nrf2 signaling pathway. Treatment with oxaliplatin enhanced the effects of erastin on CRC cells by promoting ferroptosis and oxidative stress and inhibiting cell viability. In conclusion, oxaliplatin induced ferroptosis and oxidative stress in CRC cells by inhibiting the Nrf2 signaling pathway.