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Autor(en) / Beteiligte
Titel
Regorafenib inhibited gastric cancer cells growth and invasion via CXCR4 activated Wnt pathway
Ist Teil von
  • PloS one, 2017-05, Vol.12 (5), p.e0177335-e0177335
Ort / Verlag
United States: Public Library of Science
Erscheinungsjahr
2017
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
  • Regorafenib is an oral small-molecule multi kinase inhibitor. Recently, several clinical trials have revealed that regorafenib has an anti-tumor activity in gastric cancer. However, only part of patients benefit from regorafenib, and the mechanisms of regorafenib's anti-tumor effect need further demonstrating. In this study, we would assess the potential anti-tumor effects and the underlying mechanisms of regorafenib in gastric cancer cells, and explore novel biomarkers for patients selecting of regorafenib. The anti-tumor effects of regorafenib on gastric cancer cells were analyzed via cell proliferation and invasion. The underlying mechanisms were demonstrated using molecular biology techniques. We found that regorafenib inhibited cell proliferation and invasion at the concentration of 20μmol/L and in a dose dependent manner. The anti-tumor effects of regorafenib related to the decreased expression of CXCR4, and elevated expression and activation of CXCR4 could reverse the inhibition effect of regorafenib on gastric cancer cells. Further studies revealed that regorafenib reduced the transcriptional activity of Wnt/β-Catenin pathway and led to decreased expression of Wnt pathway target genes, while overexpression and activation of CXCR4 could attenuate the inhibition effect of regorafenib on Wnt/β-Catenin pathway. Our findings demonstrated that regorafenib effectively inhibited cell proliferation and invasion of gastric cancer cells via decreasing the expression of CXCR4 and further reducing the transcriptional activity of Wnt/β-Catenin pathway.
Sprache
Englisch
Identifikatoren
ISSN: 1932-6203
eISSN: 1932-6203
DOI: 10.1371/journal.pone.0177335
Titel-ID: cdi_plos_journals_1897668857
Format
Schlagworte
Adenocarcinoma, Agar, AKT protein, American Type Culture Collection, Analysis, Angiogenesis, Angiogenesis inhibitors, Anticancer properties, Antineoplastic Agents - pharmacology, Antitumor activity, Apoptosis, Assaying, Atmosphere, Autocrine signalling, Bevacizumab, Biocompatibility, Biology and Life Sciences, Biomaterials, Biomedical materials, Biotechnology, Bone cancer, Bone marrow, Cancer, Carbon dioxide, Care and treatment, Cell growth, Cell Line, Tumor, Cell Proliferation - drug effects, Chemokines, Colonies, Colorectal carcinoma, Computer programs, Cotton, Dosage and administration, Drug resistance, Emergencies, Enzyme inhibitors, Females, Gastric cancer, Growth factors, Humans, Hypoxia, Inactivation, Incidence, Infections, Inhibitor drugs, Inhibitors, Inserts, Intestine, Kinases, Ligands, Liver, Liver cancer, Males, Medical prognosis, Medicine, Medicine and Health Sciences, Metastases, Metastasis, Methanol, Molecular biology, Oncology, Osteosarcoma cells, Pharmacology, Phenylurea Compounds - pharmacology, Physiological aspects, Positive feedback, Proteins, Pyridines - pharmacology, Reagents, Receptors, CXCR4 - metabolism, Regorafenib, Research and Analysis Methods, Ribonucleic acid, RNA, Stem cells, Stomach - drug effects, Stomach - metabolism, Stomach - pathology, Stomach cancer, Stomach Neoplasms - drug therapy, Stomach Neoplasms - metabolism, Stomach Neoplasms - pathology, Studies, Surgery, Surgical implants, Survival, Targeted cancer therapy, Tissue culture, Tumor cells, Tumors, Vascular endothelial growth factor, Wnt proteins, Wnt Signaling Pathway - drug effects

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