Toosendanin inhibits the malignant biological behaviors of esophageal squamous cell carcinoma KYSE150 cells by downregulating HIF1A expression via the AKT/mTOR pathway
10.3872/j.issn.1007-385x.2025.07.007
- VernacularTitle:川楝素经AKT/mTOR通路下调HIF1A表达抑制食管鳞状细胞癌KYSE150细胞的恶性生物学行为
- Author:
Yueming CHU
1
;
Maofei ZHU
;
Hangyu JIANG
;
Qiang YUAN
;
Xing LI
;
Kang LIU
;
Lin LI
Author Information
1. 川北医学院第二临床医学院 药学部,四川 南充 637000;川北医学院 药学院,四川 南充 637000
- Publication Type:Journal Article
- Keywords:
toosendanin(TSN);
hypoxia-inducible factor 1 alpha(HIF1A);
esophageal squamous cell carcinoma(ESCC);
KYSE150 cell;
proliferation;
migration;
invasion;
AKT/mTOR pathway
- From:
Chinese Journal of Cancer Biotherapy
2025;32(7):723-730
- CountryChina
- Language:Chinese
-
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.
