Suppressing the KIF20A/NUAK1/Nrf2/GPX4 signaling pathway induces ferroptosis and enhances the sensitivity of colorectal cancer to oxaliplatin.

ABSTRACT: Oxaliplatin resistance can develop in colorectal cancer (CRC), which may involve inhibition of ferroptosis, although further research is needed to understand this potential mechanism. We evaluated CRC cells with acquired oxaliplatin resistance (HCT116-Or) or congenital resistance (H716) to determine whether a ferroptosis inducer (RSL3) or inhibitor (liproxstatin-1) could modulate the effects of oxaliplatin. The results suggested that induction of ferroptosis could significantly reverse the oxaliplatin resistance of the CRC cells. Bioinformatic and cytobiological searches also revealed that KIF20A was highly expressed in the oxaliplatin-resistant cell lines and was strongly correlated with survival among CRC patients. Silencing KIF20A enhanced cellular sensitivity to oxaliplatin both in

SUBMITTER: Yang C 

PROVIDER: S-EPMC8202845 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature