ArticleJournal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
Selective inhibition of endothelin receptor A as an anti-angiogenic and anti-proliferative strategy for human pancreatic cancer.
Article in Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer.Journal of the National Cancer Institute · 2019Pooled it
- Endothelin-axis antagonism enhances tumor perfusion in pancreatic cancer.Cancer letters · 2022Article
- A human antibody against human endothelin receptor type A that exhibits antitumor potency.Experimental & molecular medicine · 2021Article
- Endothelin Receptor Antagonists: Status Quo and Future Perspectives for Targeted Therapy.Journal of clinical medicine · 2020Review
- A novel antiangiogenic approach for adjuvant therapy of pancreatic carcinoma.Langenbeck's archives of surgery · 2011Article
- Phenotype and genotype of pancreatic cancer cell lines.Pancreas · 2010Review
- Synergistic growth inhibitory effects of the dual endothelin-1 receptor antagonist bosentan on pancreatic stellate and cancer cells.Digestive diseases and sciences · 2009Article
- Article
- Effect of endothelin-1 in esophageal squamous cell carcinoma invasion and its correlation with cathepsin B.World journal of gastroenterology · 2007Article
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endothelin-1 (ET-1) plays a major role in tumor proliferation and angiogenesis of various types of cancer acting through endothelin receptors A and B (ET(R)A and ET(R)B). The aim of this study was to analyze the ET-1/ET(R) system in human pancreatic cancer cell lines and to evaluate the effect of a selective endothelin A inhibitor in vitro and in vivo in an orthotopic mouse model. Three different human pancreatic cancer cell lines, MiaPaCa-2, AsPC-1, and Panc-1, were studied. We found that proliferation of human pancreatic carcinoma cells expressing ET(R)A was significantly reduced with a selective antagonist. Hypoxic conditions led to improved results compared to a normoxic environment (MiaPaCa-2: -53% vs. -18%; AsPC-1: -54% vs. -46%). Proliferation of ET(R)A negative Panc-1 cells was not decreased. In vivo, the selective ET(R)A inhibition resulted in reduced angiogenesis as measured by lower microvessel densities (MiaPaCa-2: -47%; AsPC-1: -55%). The blockade of ET(R)A decreased the volume (MiaPaCa-2: -87%; AsPC-1: -28%) and metastatic spread (MiaPaCa-2: -95.5%; AsPC-1: -27%) of receptor-positive tumors, thereby increasing survival in experimental pancreatic cancer. ET(R)A blockade did not show an effect on ET(R)A negative Panc-1 tumors. Therefore, targeting ET(R)A with a selective antagonist might provide a new approach to reducing proliferation and angiogenesis in human pancreatic cancer.
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