AB017. NFκB1 regulates FDX1 to facilitate elesclomol-induced cuproptosis against glioblastoma
Abstract

AB017. NFκB1 regulates FDX1 to facilitate elesclomol-induced cuproptosis against glioblastoma

Anyi Wu, Nanheng Yin, Zhipeng Xu, Jun Dong

Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, China

Correspondence to: Jun Dong, MD, PhD. Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou 215004, China. Email: dongjun@suda.edu.cn.

Background: Ferredoxin 1 (FDX1) plays key roles in promoting elesclomol-induced cuproptosis against cancer, whether it has the potential to be a new therapeutic strategy against glioblastoma has not yet been clarified.

Methods: Glioblastoma cells were treated with elesclomol (20 nM/L) and copper chloride (2 μM/L), and then cell proliferation, migration, and invasion were evaluated by CCK-8, clonogenic and transwell assay. Western blot was performed to detect the expression of cuproptosis-relating proteins FDX1, lipoylated dihydrolipoamide S-acetyltransferase (DLAT), copper transport ATPase (ATP7A), heat shock protein 70 (HSP70), apoptotic markers B cell lymphoma-2 (BCL-2) associated X protein (Bax), and BCL-2, as well as the pan-apoptotic/death markers gasdermin D (GSDMD), solute carrier family 7 member 11 (SLC7A11). The effects of knockdown and overexpression of FDX1 on cell proliferation, migration, and invasion were observed. Bioinformatic analysis was performed to predict the corresponding transcription factors regulating FDX1 expression, and verified by dual luciferase assay. The regulatory relationship between FDX1 and its transcription factors was verified by rescue experiment and further evaluated in vivo.

Results: Elesclomol had obvious inhibitory effects on the proliferation, migration, and invasion capacities of tumor cells in a dose-dependent manner. When combined with copper chloride, the inhibitory effects on tumor cells were significantly higher both in vitro and in vivo. FDX1 expression was negatively correlated with overall survival of patients. Nuclear factor κ-light-chain enhancer of activated B cell 1 (NFκB1) was the transcription factor of FDX1 verified by dual luciferase assay. Both FDX1 and NFκB1 were highly expressed in glioblastoma. Knockdown of FDX1 or NFκB1 down-regulated proliferation, migration, and invasion abilities of tumor cells, and increased after FDX1 overexpression. FDX1 expression decreased correspondingly after NFκB1 knockdown. Up-regulation of FDX1 promoted elesclomol-induced cuproptosis against glioblastoma both in vitro and in vivo. FDX1 knockdown can reverse the inhibitory effect of elesclomol on tumor cells.

Conclusions: Elesclomol inhibits glioblastoma development via inducing cuproptosis, regulated by NFκB1/FDX1 axis.

Keywords: Glioblastoma; cuproptosis; ferredoxin 1 (FDX1); nuclear factor κ-light-chain enhancer of activated B cells (NFκB1)

Acknowledgments

Funding: This work was supported by National Natural Science Foundation of China (No. 92374113).

Footnote

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cco.amegroups.com/article/view/10.21037/cco-24-ab017/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013), and animal experiments were conducted in accordance with the ethical standards of animal care and use committee and approved by Soochow University Medical College Review Board (No. SUDA20210708A03).

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the noncommercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

Cite this abstract as: Wu A, Yin N, Xu Z, Dong J. AB017. NFκB1 regulates FDX1 to facilitate elesclomol-induced cuproptosis against glioblastoma. Chin Clin Oncol 2024;13(Suppl 1):AB017. doi: 10.21037/cco-24-ab017

Article Options

Download Citation

Share