International journal of oncology, 2016-11, Vol.49 (5), p.1890-1898
2016
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Metformin inhibits the radiation-induced invasive phenotype of esophageal squamous cell carcinoma
- Ist Teil von
- International journal of oncology, 2016-11, Vol.49 (5), p.1890-1898
- Ort / Verlag
- Greece: D.A. Spandidos
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Esophageal cancer is one of the most aggressive tumor types because of its invasiveness and metastatic potential. Several reports have described an association between increased invasiveness after ionizing radiation (IR) treatment and epithelial-to-mesenchymal transition (EMT). The biguanide metformin is reported to prevent transforming growth factor-β (TGF-β)-induced EMT and proliferation of cancer. This study examined whether IR induces EMT and promotes the invasive potential of TE-9 esophageal squamous cell carcinoma cells and the effect of metformin on IR-induced EMT. After IR exposure, TE-9 cells showed a spindle-shaped morphology and lost cell-cell adhesion. Immunoblotting showed that IR induced expression of mesenchymal markers (vimentin and N-cadherin), transcription factors (Slug, Snail, and Twist), and matrix metalloproteinases. A scratch wound assay and Matrigel invasion assay showed that IR enhanced the invasive potential and migratory capacity of TE-9 cells. Expression of hypoxia-related factor-1α and TGF-β was increased after IR. IR also induced phosphorylation of Smad2 and Smad3. Metformin inhibited radiation-induced EMT-like morphological changes, and enhanced invasion and migration of TE-9 cells. Metformin inhibited IR-induced phosphorylation of Smad2 and Smad3. Although phosphorylation of AMP-activated protein kinase was enhanced by IR and metformin, phosphorylation of mammalian target of rapamycin was enhanced by IR and suppressed by metformin. These results indicated that metformin suppressed IR-induced EMT via suppression of the TGF-β-Smad phosphorylation pathway, and a part of the non-Smad pathway. Metformin might be useful to prevent IR-induced invasion and metastasis of esophageal squamous cell carcinoma.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1019-6439eISSN: 1791-2423DOI: 10.3892/ijo.2016.3676Titel-ID: cdi_proquest_journals_1932305736
- Format
- –
- Schlagworte
- Antidiabetics, Apoptosis - drug effects, Apoptosis - radiation effects, Blotting, Western, Cancer therapies, Carcinoma, Squamous Cell - drug therapy, Carcinoma, Squamous Cell - metabolism, Carcinoma, Squamous Cell - pathology, Cell Adhesion - drug effects, Cell Adhesion - radiation effects, Cell Movement - drug effects, Cell Movement - radiation effects, Cell Proliferation - drug effects, Cell Proliferation - radiation effects, Diabetes, Drug dosages, Drug therapy, Endometrial cancer, Epithelial-Mesenchymal Transition - drug effects, Epithelial-Mesenchymal Transition - radiation effects, epithelial-to-mesenchymal transition, Esophageal cancer, Esophageal Neoplasms - drug therapy, Esophageal Neoplasms - metabolism, Esophageal Neoplasms - pathology, Fluorescent Antibody Technique, Gene expression, Gene Expression Regulation, Neoplastic - drug effects, Gene Expression Regulation, Neoplastic - radiation effects, Genotype & phenotype, Glucose, Humans, Hypoglycemia, Hypoglycemic Agents - pharmacology, Insulin, Kinases, Metastasis, Metformin, Metformin - pharmacology, Neoplasm Invasiveness, Patient outcomes, Phenotype, Phosphorylation, Phosphorylation - drug effects, Phosphorylation - radiation effects, radiation, Radiation therapy, Signal Transduction - drug effects, Signal Transduction - radiation effects, Smad2 Protein - metabolism, Smad3 Protein - metabolism, Squamous cell carcinoma, Studies, Transforming Growth Factor beta - metabolism, transforming growth factor-β, Tumor Cells, Cultured, Tumors, X-Rays