Objective: To explore the pharmacological mechanism and biological pathway of triptolide (TP) in the treatment of osteosarcoma (OS). Methods: The target genes and mediated signaling pathways of TP for OS were analyzed by whole genome sequencing, topological analysis, multiple public databases as well as in vitro experiments and clinical tissues. Results: 100 nM TP could effectively inhibit the proliferation and viability of U2OS cells, inhibit cell migration and invasion, and promote apoptosis of U2OS cells (P＜0.05). The mRNA and protein expressions of NOC3 like DNA replication regulator(NOC3L)、DEAH-Box Helicase 15(DHX15)and WD repeat domain 3(WDR3) in OS and normal tissues were significantly increased by RT-qPCR and western blotting (P＜0.05), and the results showed that NOC3L, DHX15 and WDR3 were significantly increased in OS tissues (P＜0.05). After U2OS cells were treated with 100 nM TP for 24 h, RT-qPCR and Western blot results showed that the mRNA and protein expression of NOC3L, DHX15 and WDR3 were significantly decreased (P＜0.05). In addition, cell immunofluorescence labeling confirmed that 100 nM TP could effectively inhibit the expression of NOC3L, DHX15 and WDR3. The enrichment results of TP signaling pathway were mainly in Wnt signaling pathway. Western blot analysis (with GAPDH as internal reference) showed that the expression of GSK-3β and p-GSK-3β increased, and the expression of β-catenin and β-catenin (qSer) decreased (P＜0.05). Conclusion: TP inhibits OS progression by suppressing NOC3L, DHX15 and WDR3 expression and Wnt signaling pathway.
ZHANG Xiaoyong
,
XUE Xiaohui
,
SHAO Yinying
,
DING Shaocheng
,
LI Jun
,
HUANG Gan
. Inhibition of osteosarcoma progression by Triptolide via NOC3L, DHX15 and WDR3 and Wnt signalling[J]. Journal of Baotou Medical College, 2025
, 41(8)
: 36
-42
.
DOI: 10.16833/j.cnki.jbmc.2025.08.007
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