Effects of realgar-indigo naturalis formula on a zebrafish tumor xenograft model induced by human acute promyelocytic leukemia cells: antitumor activity, hepatotoxicity, and transcriptomic analysis
BackgroundLeukemia is a malignant hematologic disease that poses a serious threat to human health. Realgar-Indigo Naturalis formula (RIF), a traditional Chinese medicine formula, have demonstrated anti-tumor activity, but its mechanisms of action remain unclear.ObjectiveThis study aimed to establish...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1619352/full |
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| Summary: | BackgroundLeukemia is a malignant hematologic disease that poses a serious threat to human health. Realgar-Indigo Naturalis formula (RIF), a traditional Chinese medicine formula, have demonstrated anti-tumor activity, but its mechanisms of action remain unclear.ObjectiveThis study aimed to establish a zebrafish HL-60 tumor transplantation model to investigate the anti-leukemic effects of RIF and explore its underlying mechanisms.MethodsThe zebrafish HL-60 tumor transplantation model was established, with RIF as the intervention drug and all-trans retinoic acid (ATRA) as the control. Anti-tumor efficacy was assessed via pharmacodynamic analysis. Transcriptomic analysis further elucidated gene expression profiles, differentially expressed genes, and relevant biological pathways.ResultsRIF significantly reduced tumor cell fluorescence intensity, demonstrating anti-tumor efficacy. Additionally, it improved HL-60-induced liver damage in zebrafish, as evidenced by a reduction in fatty vacuolar degeneration in liver tissue. Transcriptomic analysis revealed that ATRA mainly affected the FoxO signaling pathway, PI3K-Akt signaling pathway, apoptosis, and complement and coagulation cascades in leukemia treatment. RIF primarily influenced the ubiquitin-proteasome system, ferroptosis, and glutathione metabolism. The combination of ATRA and RIF also affected autophagosome and lysosome pathways, in addition to the aforementioned pathways.ConclusionRIF exhibit significant anti-tumor effects through modulation of multiple pathways. This study provides a theoretical foundation for the potential clinical application of RIF in leukemia treatment. |
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| ISSN: | 1663-9812 |