Study on the CHJ01 antitumor activity and mechanism via targeting sphingosine kinase 1 in A549 cells

Abstract

The SphK1 inhibitor development is of great importance for the treatment of non-small cell lung cancer (NSCLC). In this study, CHJ01 which has been previously shown anti-tumor effects was introduced to investigate the detailed antitumor mechanism both in vitro and in vivo. CHJ01 inhibited the A549 cell proliferation, migration, and invasion significantly and showed cytotoxicity to A549. CHJ01 induced G0/G1 cell cycle arrest by increasing ceramide levels and altered the expression of TRAF2, Bcl-2, Bax and RELA. CHJ01 inhibited the TRAF2/NF-кB signaling pathway and promoted apoptosis by downregulating Bcl-2 and upregulating Bax. In vivo anti-tumor effects were investigated using a nude mouse ectopic tumor model. CHJ01 reduced the volumes and weights of xenograft tumor in nude mice. CHJ01 induced apoptosis by HE staining and immunohistochemistry assay. These results indicated that CHJ01 can be a potential candidate for the treatment of NSCLC.

Keywords

CHJ01 / Sphingosine kinase 1 / A549 / TRAF2/NF-κB signaling pathway / Apoptosis / Non-small cell lung cancer / NSCLC

CRediT authorship contribution statement

Caiyu Liu: Writing - review & editing, Writing - original draft, Visualization, Validation, Software, Resources, Investigation, Formal analysis, Data curation. Shengmei Gao: Writing - original draft, Validation, Software, Formal analysis. Bo Liu: Resources, Investigation, Funding acquisition. Feipeng Zhang: Software, Resources. Yanling Mu: Validation, Project administration, Methodology. Fuwen Wang: Writing - review & editing, Validation, Supervision, Resources, Methodology, Investigation, Conceptualization. Yan Li: Writing - review & editing, Writing - original draft, Supervision, Project administration, Methodology, Investigation, Funding acquisition, Conceptualization.

Data availability statement

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Compliance with ethics guidelines

Caiyu Liu, Shengmei Gao, Bo Liu, Feipeng Zhang, Yanling Mu, Fuwen Wang and Yan Li declare that they have no conflicts of interest.

All institutional and national guidelines for the care and use of laboratory animals were followed. The animal study protocol was approved by Ethics Com-mittee of Institute of Materia Medica Shandong Academy of Medical Sciences (protocol code AEC2021097 and June 2021).

Declaration of generative AI in scientific writing

Not applicable.

Funding information

This research was funded by Natural Science Foundation of Shandong Provincial, grant number ZR2023MB080. Open Project of Shandong Key Laboratory of Glycochemistry and Biology, Shandong University, grant number 2023CCG05. Natural Science Foundation of Shandong Provincial, grant number ZR2023QH129.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

We are indebted to our principle collaborators at Shandong First Medical University.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi.org/10.1016/j.pscia.2025.100077.

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