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Metformin suppresses hypoxia-inducible factor-1 α expression in cancer-associated fibroblasts to block tumor-stromal cross-talk in breast cancer
Ist Teil von
Nan fang yi ke da xue xue bao = Journal of Southern Medical University, 2024-03, Vol.44 (3), p.428
Ort / Verlag
China
Erscheinungsjahr
2024
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
To investigate the mechanism of metformin for regulating tumor-stromal cell cross-talk in breast cancer.
Tumor associated fibroblasts (CAFs) co-cultured with breast cancer cells were treated with metformin, and the changes in expressions of hypoxia-inducible factor-1
(HIF-1
), p-AMPK, stroma-derived factor-1 (SDF-1) and interleukin-8 (IL-8) in the CAFs were detected using ELISA, RT-qPCR or Western blotting; Transwell assay was used to evaluate the invasiveness of the tumor cells and its changes following treatment with exogenous SDF-1, IL-8 and TGF-β1. The effects of HIF-1
shRNA or overexpression plasmid, AMPK shRNA, and treatment with OG (a proline hydroxylase inhibitor) or 2-OXO (a proline hydroxylase activator) were examined on p-AMPK, HIF-1
, SDF-1 and IL-8 expressions and invasiveness of the CAFs.
Metformin treatment significantly increased the expression levels of p-AMPK, SDF-1 and IL-8 (
<0.05) and decreased HIF-1
expression (
<0.05) without affecting AMPK expression level (
>0.05) in the CAFs. The inv