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Norcantharidin inhibits the proliferation of small cell lung cancer H446 cells via Nrf2/HO-1 pathway mediated ferroptosis

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2025 04
Page:
583-589
Research Field:
Publishing date:

Info

Title:
Norcantharidin inhibits the proliferation of small cell lung cancer H446 cells via Nrf2/HO-1 pathway mediated ferroptosis
Author(s):
SU Fan; LIU Dan; DENG Shukai
Department of Respiratory and Critical Care Medicine,Affiliated Hospital of Southwest Medical University,Sichuan Luzhou 646000,China.
Keywords:
small cell lung cancer; norcantharidin; ferroptosis; Nrf2/HO-1 pathway
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2025.04.006
Abstract:
Objective:To investigate the effect of norcantharidin (NCTD) on the proliferation of small cell lung cancer H446 cells,and to study the correlation between the proliferation of H446 cells and ferroptosis.Methods:H446 cells were treated with gradient concentrations of NCTD (0,2,4,8,16,32,64 μg/mL) for 24 h,48 h,and 72 h.The effect of NCTD on cell proliferation was detected by CCK-8 assay,and the median inhibitory concentration (IC50) was calculated for subsequent experiments.The experiment was divided into control group,NCTD group and NCTD+Fer-1 group.The ultrastructural morphological changes of mitochondria were observed by transmission electron microscopy.The level of reactive oxygen species (ROS) in the cells was detected by flow cytometry,and the expression of Fe2+ was detected by FerroOrange fluorescent probe kit.Protein expression level of ferroptosis-related recombinant solute carrier family 7 member 11 (SLC7A11),glutathione peroxidase 4 (GPX4),nuclear factor erythroid 2-related factor 2 (Nrf2),and heme oxygenase-1 (HO-1) in H446 cells was detected by Western blot.Results:The proliferation of H446 cells was inhibited by NCTD in a time and concentration dependent manner (P＜0.05).Typical morphological changes of ferroptosis induced by NCTD were observed under transmission electron microscopy.NCTD up-regulated the intracellular Fe2+ and ROS levels,while down-regulated the expression of ferroptosis inhibitory proteins SLC7A11,GPX4,Nrf2 and HO-1 (P＜0.05).These changes could be reversed by ferroptosis inhibitor Ferrostatin-1 （Fer-1）.Conclusion:NCTD could inhibit the proliferation of H446 cells,which may induce ferroptosis by down-regulating the expression of Nrf2/HO-1 pathway,increasing intracellular Fe2+ and ROS levels.

References:

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