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Archive > Volume 32 Issue 7 > 2025,32(7):723-730. DOI:10.3872/j.issn.1007-385X.2025.07.007 Prev Next
Basic Research
Toosendanin inhibits the malignant biological behaviors of esophageal squamous cell carcinoma KYSE150 cells by downregulating HIF1A expression via the AKT/ mTOR pathway
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Abstract:
[Abstract] Objective: To investigate the effects of toosendanin (TSN) on the proliferation, apoptosis, migration and invasion of esophageal squamous cell carcinoma (ESCC) KYSE150 cells, and to elucidate its underlying molecular mechanisms. Methods: CCK-8 assay, colony formation assay, and EdU assay were used to assess the effects of varying TSN concentrations (0.062 5, 0.125, and 0.25 μmol/L) on KYSE150 cell proliferation. The impacts of TSN on the apoptosis, migration, and invasion of KYSE150 cells were evaluated using flow cytometry, wound healing assay, and Transwell chamber assay, respectively. The expression of hypoxia-inducible factor 1 alpha (HIF1A) in esophageal cancer tissues was analyzed using the GEPIA database. qPCR was used to detect the expression level of HIF1A mRNA in human esophageal epithelial Het-1A and KYSE150 cells, and in TSN-treated KYSE150 cells. Western blot (WB) was performed to detect the effects of TSN on the upstream signaling pathway AKT/mTOR of HIF1A and the expression of downstream proteins related to cell migration, invasion, and apoptosis. Results: TSN of varying concentrations significantly inhibited proliferation, migration, and invasion of KYSE150 cells and promoted apoptosis in a dose-dependent manner (P < 0.05 or P < 0.01). HIF1A mRNA was highly expressed in KYSE150 cells, and its expression was significantly downregulated after TSN treatment (P < 0.05 or P < 0.01). TSN markedly downregulated the expression of HIF1A and key upstream signaling proteins p-AKT and p-mTOR. In addition, TSN significantly suppressed the expression of downstream proteins associated with cell migration, invasion, and apoptosis, including N-cadherin, vimentin, Bcl-2, and caspase-3, while upregulating the expression of E-cadherin (P < 0.05 or P < 0.01). Conclusion: TSN inhibits the proliferation, migration, and invasion, and induces apoptosis in ESCC KYSE150 cells by down-regulating HIF1A expression through suppression of the AKT/mTOR signaling pathway.
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