Work

Triptolide combined with arsenic trioxide induces apoptosis of myelodysplastic syndrome cells by inhibiting the NF-κB signaling pathway

Year: 2025

Type: article

Abstract: BACKGROUND: The aim of this study was to delve into the combined effects of triptolide (TL) and arsenic trioxide (ATO) on the proliferation and apoptosis of myelodysplastic syndrome (MDS) cells, in addition to exploring the important role of the NF-κB signaling pathway underlying these combined actions. METHODS: The MDS cells SKM-1 were treated with TL, ATO, and TL combined with ATO, respectively. The CCK-8 kit was used to detect proliferation viability in each group. Flow cytometry with Annexin V-FITC/PI double staining was employed to investigate the rate of apoptosis. The expression levels of mRNA and proteins related to apoptotic molecules, along with key molecules of the NF-κB signaling pathway, were meticulously detected in each group by real-time quantitative polymerase chain reaction and western blot. RESULTS: TL in combination with ATO exhibited a pronounced inhibitory effect on the proliferation of SKM-1 cells (P<.0001), and the combined actions also triggered apoptosis in SKM-1 cells. The proliferation inhibition rate and apoptosis rate of the combined treatment group were significantly elevated compared to those of the individual drug groups (P<.05). Upon the integration of TL and ATO, the concentration of PARP cleavage protein escalates, and the mRNA and protein expressions of the executioner caspase, including Caspase3 and Caspase8, experience a marked elevation. Conversely, the mRNA and protein expressions of the anti-apoptotic genes Bcl-2, Bcl-XL, and cIAP1 undergo a significant reduction. CONCLUSION: The combined impact of TL and ATO amplifies the expression of p65 within the canonical NF-κB signaling pathway, while inhibiting the expression of IkBα, p52, and RelB in the noncanonical pathway. The combination effect of TL and ATO markedly suppresses the proliferation of MDS cells and induces apoptosis collaboratively, which potentially occurs through a mechanism by inhibiting the NF-κB signaling pathway.

Source: Medicine

DOI: 10.1097/md.0000000000046206