[Exploring mechanism of gypenosides in inhibiting anoikis resistance in breast cancer via TGF-β1/Foxp3/RORγt signaling axis]

作者：Liu DG, Li ZR, Shu Y, Li JQ, Dong WT, Liu Q · 发表于：Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica · 年份：2026 · DOI：10.19540/j.cnki.cjcmm.20260227.901 · 研究领域：Transforming Growth Factor beta1、Anoikis、Forkhead Transcription Factors、Nuclear Receptor Subfamily 1, Group F, Member 3、Breast Neoplasms、Gynostemma、Drugs, Chinese Herbal、Humans、Female、Animals、Signal Transduction、Mice

This study investigated the effect of gypenosides(GPs) on anoikis resistance(AR) in human triple-negative breast cancer(TNBC) MDA-MB-231 cells and explored the underlying mechanism involving the transforming growth factor β1(TGF-β1)/forkhead box protein P3(Foxp3)/retinoic acid-related orphan receptor γt(RORγt) signaling axis. An anoikis model was established using poly-HEMA coated plates, and cells were divided into normal adherent, anoikis model, GPs(100 μg·mL~(-1)), TGF-β1 inhibitor(LY, 10 μmol·L~(-1)), and GPs + LY groups. Cell viability, apoptosis, invasion and migration were assessed by CCK-8 assay, flow cytometry with AnnexinV-FITC/PI staining, and Transwell assay, respectively. The mRNA and protein expression levels of TGF-β1, Foxp3, RORγt, B-cell Lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), cysteine aspartic acid specific protease-3(caspase-3), and Smad2/3 phosphorylation levels were measured by quantitative real-time PCR(qRT-PCR) and Western blot. Nuclear localization of Foxp3 and RORγt was examined by immunofluorescence staining. A breast cancer bone metastasis model was established in nude mice by tail vein injection. After intervention, the circulating tumor cells(CTCs) in peripheral blood and the formation of bone metastasis foci were evaluated. The mRNA and protein expression levels of TGF-β1, Foxp3, RORγt in bone metastasis foci of each nude mouse breast cancer bone metastasis model were detected using qRT-PCR and Western blot. In vitro experimental resu...