Effects and mechanisms of the kidney-reinforcing and blood circulation-activating and collateral dredging decoction metabolites on the proliferation of multiple myeloma KM3 cells
10.3760/cma.j.cn121090-20241209-00547
- VernacularTitle:补肾活血通络方代谢产物对多发性骨髓瘤KM3细胞增殖的影响及其作用机制
- Author:
Jingbo SHI
1
;
Changnian LI
;
Wenjian WEI
;
Jiyuan DING
;
Guodong MA
;
Lulu LI
;
Yaru WANG
;
Yitong LU
;
Jie XU
;
Wei ZHENG
;
Yan WANG
;
Jingyi WANG
;
Ruirong XU
;
Siyuan CUI
Author Information
1. 山东中医药大学第一临床医学院，济南 250014
- Publication Type:Journal Article
- Keywords:
Multiple myeloma;
Mitochondrial dynamics;
Autophagy;
Network pharmacology
- From:
Chinese Journal of Hematology
2025;46(7):647-654
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the effects and underlying mechanisms of metabolites derived from the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction on the proliferation of multiple myeloma (MM) KM3 cells.Methods:MM KM3 cells in the logarithmic growth phase were treated with 3%, 6%, 9%, or 12% metabolites of kidney-reinforcing, blood circulation-activating, and collateral dredging decoction. Cell viability was assessed using the CCK-8 assay. Apoptosis and necrosis were evaluated using flow cytometry and TUNEL staining. Mitochondrial and cellular ultrastructural changes were examined using transmission electron microscopy. mRNA and protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (MFF), PTEN-induced kinase 1 (Pink1), and E3 ubiquitin ligase (Parkin) were determined through quantitative real-time PCR and western blotting. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with network pharmacology, was utilized for reverse verification of the pharmacodynamic mechanisms and therapeutic targets underlying the anti-MM activity of this decoction.Results:The metabolites of the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction inhibited KM3 cell proliferation and induced apoptosis in a dose-dependent manner. Transmission electron microscopy revealed increased mitochondrial fission and autophagic structures, with effects intensifying at higher metabolite concentrations. mRNA and protein expression of Drp1, Fis1, MFF, Pink1, and Parkin were significantly upregulated in treatment groups compared to controls ( P<0.05), with the most pronounced effects observed in the 12% metabolite group ( P<0.01). HPLC-MS/MS identified 121 bioactive compounds in BHTF, which shared 474 overlapping targets with MM. Enrichment analysis suggested that BHTF exerts antitumor effects primarily through apigenin, palmatine, and other key components by modulating TNF, NF-κB, and mitophagy pathways. Conclusion:The kidney-reinforcing and blood circulation-activating and collateral dredging decoction suppresses the proliferation of MM KM3 cells, potentially through mechanisms involving the regulation of mitochondrial dynamics and induction of autophagy.
