ArticleCancer science2006
Sivelestat, a specific neutrophil elastase inhibitor, suppresses the growth of gastric carcinoma cells by preventing the release of transforming growth factor-alpha.
Article in Cancer science, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 52 citations in OpenAlex.
- Neutrophil elastase inhibitor (sivelestat) preserves antitumor immunity and reduces the inflammatory mediators associated with major surgery.Surgery today · 2007Trial
- Neutrophil Extracellular Traps in the Tumor Microenvironment: Mechanisms, Immune Regulation, and Implications for Immune Checkpoint Inhibitor Therapy.International journal of molecular sciences · 2026Review
- Neutrophil serine proteases inhibit thermogenic capacity of visceral white adipose tissue.Nature metabolism · 2026Article
- Neutrophils and neutrophil extracellular traps: double-edged swords in cancer pathophysiology and therapy resistance.Cell communication and signaling : CCS · 2025Review
- The heterogeneous roles of neutrophils in gastric cancer: scaffold or target?Cellular & molecular biology letters · 2025Review
- Downregulation of tropomyosin 2 promotes the progression of lung adenocarcinoma by regulating neutrophil infiltration through neutrophil elastase.Cell death & disease · 2025Article
- Imaging and Therapy of Tumors Based on Neutrophil Extracellular Traps.Small science · 2024Article
- Targeting neutrophil elastase is a promising direction for future cancer treatment.Discover oncology · 2024Review
- Neutrophil Elastase Remodels Mammary Tumors to Facilitate Lung Metastasis.Molecular cancer therapeutics · 2024Article
- Neutrophils and neutrophil extracellular traps in cancer: promising targets for engineered nanomaterials.Drug delivery and translational research · 2023Review
- Neutrophil elastase: From mechanisms to therapeutic potential.Journal of pharmaceutical analysis · 2023Review
- Neutrophil Extracellular Traps Promote Metastases of Colorectal Cancers through Activation of ERK Signaling by Releasing Neutrophil Elastase.International journal of molecular sciences · 2023Article
- Tumor-associated neutrophils in pancreatic cancer progression and metastasis.American journal of cancer research · 2023Review
- Neutrophil Elastase-Activatable Prodrugs Based on an Alkoxyamine Platform to Deliver Alkyl Radicals Cytotoxic to Tumor Cells.Journal of medicinal chemistry · 2022Article
- Tumor-associated macrophages, dendritic cells, and neutrophils: biological roles, crosstalk, and therapeutic relevance.Medical review (2021) · 2021Review
- Human Antibody Domains and Fragments Targeting Neutrophil Elastase as Candidate Therapeutics for Cancer and Inflammation-Related Diseases.International journal of molecular sciences · 2021Article
- Neutrophil Elastase Facilitates Tumor Cell Intravasation and Early Metastatic Events.iScience · 2020Article
- Neutrophils in the Tumor Microenvironment.Advances in experimental medicine and biology · 2020Review
- Targeting High Mobility Group Box-1 (HMGB1) Promotes Cell Death in Myelodysplastic Syndrome.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Tumor-Associated Neutrophils in Cancer: Going Pro.Cancers · 2019Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neutrophil elastase is a neutral serine proteinase produced by polymorphonuclear leukocytes and monocytes/macrophages, especially under surgical stress. In the present study, we investigated whether NE promotes cell growth by activation of EGFR to elucidate whether surgical stress induces tumor proliferation and progression. Furthermore, we examined the antitumor effect of a specific NE inhibitor, sivelestat. Cell growth assays were carried out in vitro and in vivo using TMK-1 gastric cancer cells. TMK-1 cell growth was stimulated to 118% of that of the control cells after 48 h stimulation with 1 microg/mL NE according to an MTT assay. Sivelestat inhibited cell growth to 23.4 and 58.0% of control values at concentrations of 100 and 1,000 microg/mL, respectively. NE rapidly phosphorylated EGFR in only 5 min and triggered the ERK1/2-mitogenic signaling pathway in TMK-1. It was further demonstrated that NE-induced EGFR phosphorylation was transactivated through TGF-alpha, using ELISA. NE increased the cleavage of TGF-alpha from the cell surface 30-fold compared with the cells without treatment. Interestingly, sivelestat significantly reduced NE-induced EGFR phosphorylation and ERK1/2 activation and completely blocked the release of TGF-alpha from the TMK-1 cell surface. In a xenograft study, the addition of ventrotomy as a surgical stress promoted tumor growth. Sivelestat significantly suppressed the tumor growth induced by surgical stress. These results indicate that sivelestat suppresses the growth of gastric cancer cells by inhibiting the release of TGF-alpha stimulated by NE, which often occurs after surgical stresses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.