24-dehydrocholesterol reductase facilitates cisplatin resistance of non-small cell lung cancer via repressing reactive oxygen species/ferroptosis pathway

Background: non-small-cell lung cancer (nsclc) remains a deadly malignancy worldwide. resistance to cisplatin (ddp) is a significant obstacle that limits the therapeutic efficacy in nsclc patients. objectives: this study investigated the role and mechanism of 24-dehydrocholesterol reductase (dhcr24) in ddp resistance in nsclc cells. methods: 24-dehydrocholesterol reductase levels, ferroptosis-related molecules, and proteins involved in the pi3k/akt/gsk3β pathway were measured. the growth capacity of the cells was evaluated, and ferroptosis was assessed by measuring mda, gsh, fe 2+, and ros levels. the impact of dhcr24 on nsclc ddp resistance was analyzed using a tumor xenograft assay in vivo. ki-67 and dhcr24 expression in tumors were evaluated through immunohistochemical staining. results: 24-dehydrocholesterol reductase expression was elevated in ddp-resistant cells, indicating a poorer prognosis for nsclc patients. down-regulation of dhcr24 inhibited the growth of ddp-resistant cells and induced ferroptosis. inhibition of dhcr24 led to the inactivation of the pi3k/akt/gsk3β pathway and subsequent induction of ferroptosis. inhibition of ferroptosis or activation of the pi3k/akt/gsk3β pathway counteracted the increased ddp sensitivity induced by dhcr24 knockdown in nsclc cells. additionally, dhcr24 deficiency improved nsclc ddp resistance in vivo. conclusions: 24-dehydrocholesterol reductase contributes to ddp resistance in nsclc cells by suppressing ferroptosis through the activation of the pi3k/akt/gsk3β pathway.