Salinomycin sodium exerts anti diffuse large B-cell lymphoma activity through inhibition of LRP6-mediated Wnt/β-catenin and mTORC1 signaling

Abstract

Low-density lipoprotein receptor-related protein-6 (LRP6) is overexpressed in various cancers. The small molecule salinomycin sodium inhibits LRP6. We observed a higher proportion of subjects with non-germinal center B (non-GCB) subtypes having high LRP6 expression than those with GCB subtypes by immunohistochemistry. The PCR and Western blot assays demonstrated increased LRP6 expression in non-GCB subtype cells. In addition, CCK-8 assays and transwell cell migration assays revealed that salinomycin sodium exhibited dose- and time-dependent inhibition of proliferation and migration in non-GCB subtype cells. Furthermore, Western blot assays showed that salinomycin sodium decreased the expression of Bcl2, while increasing the expression of Bax. Additionally, salinomycin sodium suppressed LRP6 expression, blocked LRP6 phosphorylation, and inhibited the Wnt/β-catenin and mTORC1 signaling pathways. Our results suggest that LRP6 is highly expressed in non-GCB subtype. Furthermore, salinomycin sodium inhibited LRP6 expression and the Wnt/β-catenin and mTORC1 signaling in non-GCB subtype cells, and displayed potent anticancer activity.

Keywords:

• Salinomycin sodium
• LRP6
• Wnt/β-catenin signaling
• mTORC1 signaling
• diffuse large B-cell lymphoma

Acknowledgments

The authors thank the Central Laboratory of The First Hospital of Lanzhou University for providing the experimental platform for this work.

Additional information

Funding

This work was supported by Natural Sciences Foundation of Gansu Province (21JR11RA107) and the Hospital Foundation of The First Hospital of Lanzhou University (ldyyn2019-21).