24-Dehydrocholesterol Reductase Facilitates Cisplatin Resistance of Non-small Cell Lung Cancer via Repressing Reactive Oxygen Species/Ferroptosis Pathway
| Author | Ce Qin | en |
| Author | Jun Yuan | en |
| Author | Rui Zhang | en |
| Author | Li Liu | en |
| Author | Yue-Song Ban | en |
| Orcid | Ce Qin [0009-0004-2314-4661] | en |
| Issued Date | 2024-12-31 | en |
| Abstract | 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, Fe2+, 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. | en |
| DOI | https://doi.org/10.5812/ijpr-150017 | en |
| Keyword | DHCR24 | en |
| Keyword | NSCLC | en |
| Keyword | Cisplatin Resistance | en |
| Keyword | Ferroptosis, PI3K/AKT/GSK3β Pathway | en |
| Publisher | Brieflands | en |
| Title | 24-Dehydrocholesterol Reductase Facilitates Cisplatin Resistance of Non-small Cell Lung Cancer via Repressing Reactive Oxygen Species/Ferroptosis Pathway | en |
| Type | Research Article | en |