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| Mechanism study of Qinghuang Powder components combination on proliferation and apoptosis intervention in acute promyelocytic leukemia |
| Hits 457 Download times 225 Received:April 09, 2025 |
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| DOI
10.11656/j.issn.1672-1519.2025.07.14 |
| Key Words
Qinghuang Powder components;acute promyelocytic leukemia;synergistic effect;multi-omics integrated analysis;PI3K/AKT signaling pathway;apoptosis of cell |
| Author Name | Affiliation | E-mail | | ZHANG Yue | Department of Traditional Chinese and Western Medicine, Qingdao University, Qingdao 266000, China | scgdoctor@126.com | | SUN Changgang | Department of Traditional Chinese and Western Medicine, Qingdao University, Qingdao 266000, China
Weifang Hospital of Traditional Chinese Medicine, Shandong Second Medical University, Weifang 261041, China | |
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| Abstract
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| [Objective] To validate the synergistic effects of Qinghuang Powder components combination on acute promyelocytic leukemia（APL） and elucidate its molecular mechanisms through multi-omics integrated analysis. [Methods] CCK-8 assay was used to determine the inhibitory activity of Indirubin and Arsenic disulfide（As2S2） on NB4 cells，and their synergistic effects were evaluated using the Chou-Talalay model. Cell morphological changes were observed by Giemsa staining，while cell apoptosis rate and cycle distribution were detected by flow cytometry. Drug-disease targets were screened through multiple databases integration，followed by GO and KEGG analyses. Transcriptome sequencing was employed to identify differentially expressed genes with subsequent bioinformatics analysis. Western blot was used to verify key protein expression changes. [Results] Indirubin and As2S2 exhibited dose-dependent inhibition on NB4 cells. Chou-Talalay analysis confirmed significant synergistic effects（CI<1） between Indirubin（80 μmol/L） and As2S2（16 μmol/L）. The drug combination promoted cell apoptosis and increased the proportion of cells in G0/G1 phase（P＜0.05）. Integrated database analysis identified 44 key targets，while transcriptome sequencing revealed 1 767 differentially expressed genes，both enriched in pathways including PI3K/AKT signaling. Western blot confirmed that the drug combination inhibited PI3K/AKT phosphorylation（P＜0.05） and increased the BAX/BCL2 ratio，verifying PI3K/AKT pathway as a key target for Qinghuang Powder components against APL. [Conclusion] Qinghuang Powder components combination exerts anti-APL effects through synergistic inhibition of the PI3K/AKT signaling pathway，regulating cell cycle and promoting apoptosis，thus providing a molecular pharmacological basis for clinical application. |
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