PUBLICATION
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
- Authors
- Bai, D., Zhang, Z., Gao, J., Wang, Q., Macdonald, R., Xu, Z., Chen, S., Huang, N., Luo, L.
- ID
- ZDB-PUB-250805-6
- Date
- 2025
- Source
- Frontiers in pharmacology 16: 16193521619352 (Journal)
- Registered Authors
- Keywords
- Realgar-Indigo naturalis formula (RIF), all-trans retinoic acid, leukemia, transcriptomic analysis, zebrafish
- MeSH Terms
- none
- PubMed
- 40756980 Full text @ Front Pharmacol
Citation
Bai, D., Zhang, Z., Gao, J., Wang, Q., Macdonald, R., Xu, Z., Chen, S., Huang, N., Luo, L. (2025) 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. Frontiers in pharmacology. 16:16193521619352.
Abstract
Background Leukemia 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.
Objective This study aimed to establish a zebrafish HL-60 tumor transplantation model to investigate the anti-leukemic effects of RIF and explore its underlying mechanisms.
Methods The 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.
Results RIF 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.
Conclusion RIF 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping