ArticleRedox biology2019
Role of nitric oxide in pancreatic cancer cells exhibiting the invasive phenotype.
Article in Redox biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Nitric oxide-dependent stabilization of vimentin confers chemoresistance in ovarian cancer.Molecular therapy. Nucleic acids · 2026Article
- Loss of inducible nitric oxide synthase promotes Kras/Pten-driven lung tumorigenesis.Frontiers in cell and developmental biology · 2026Article
- ATPase copper transporting beta attenuates malignant features with high expression as an indicator of favorable prognosis in breast cancer.Breast cancer (Tokyo, Japan) · 2025Article
- Regulation and Pharmacology of the Cyclic GMP and Nitric Oxide Pathway in Embryonic and Adult Stem Cells.Cells · 2024Review
- Deconvoluting nitric oxide-protein interactions with spatially resolved multiplex imaging.Chemical science · 2024Article
- Triple targeting of mutant EGFRJournal of enzyme inhibition and medicinal chemistry · 2023Article
- Synthesis of new multitarget-directed ligands containing thienopyrimidine nucleus for inhibition of 15-lipoxygenase, cyclooxygenases, and pro-inflammatory cytokines.European journal of medicinal chemistry · 2023Article
- Metagenomic analysis unveils the microbial landscape of pancreatic tumors.Frontiers in microbiology · 2023Article
- The Chemical Biology of NO that Regulates Oncogenic Signaling and Metabolism: NOS2 and Its Role in Inflammatory Disease.Critical reviews in oncogenesis · 2023Review
- Membrane-camouflaged supramolecular nanoparticles for co-delivery of chemotherapeutic and molecular-targeted drugs with siRNA against patient-derived pancreatic carcinoma.Acta pharmaceutica Sinica. B · 2022Article
- Gasotransmitters in the tumor microenvironment: Impacts on cancer chemotherapy (Review).Molecular medicine reports · 2022Review
- Article
- Design and synthesis of novel quinazolinones conjugated ibuprofen, indole acetamide, or thioacetohydrazide as selective COX-2 inhibitors: anti-inflammatory, analgesic and anticancer activities.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Novel 1,2,4-triazine-quinoline hybrids: The privileged scaffolds as potent multi-target inhibitors of LPS-induced inflammatory response via dual COX-2 and 15-LOX inhibition.European journal of medicinal chemistry · 2021Article
- New possible silver lining for pancreatic cancer therapy: Hydrogen sulfide and its donors.Acta pharmaceutica Sinica. B · 2021Review
- The Role of Nitric Oxide in Cancer: Master Regulator or NOt?International journal of molecular sciences · 2020Review
- Relevance of iNOS expression in tumor growth and maintenance of cancer stem cells in a bladder cancer model.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Article
- Nitric Oxide and S-Nitrosylation in Cancers: Emphasis on Breast Cancer.Breast cancer : basic and clinical research · 2020Review
- Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Pancreatic cancer is a highly metastatic tumor with an extremely low 5-year survival rate. Lack of efficient diagnostics and dearth of effective therapeutics that can target the cancer as well as the microenvironment niche are the reasons for limited success in treatment and management of this disease. Cell invasion through extracellular matrix (ECM) involves the complex regulation of adhesion to and detachment from ECM and its understanding is critical to metastatic potential of pancreatic cancer. To understand the characteristics of these cancer cells and their ability to metastasize, we compared human pancreatic cancer cell line, PANC-1 and its invading phenotype (INV) collected from transwell inserts. The invasive cell type, INV, exhibited higher resistance to Carbon-ion radiation compared to whole cultured (normally dish-cultured) PANC-1 (WCC), and had more efficient in vitro spheroid formation capability. Invasiveness of INV was hampered by nitric oxide synthase (NOS) inhibitors, suggesting that nitric oxide (NO) plays a cardinal role in PANC-1 invasion. In addition, in vitro studies indicated that a MEK-ERK-dependent, JAK independent mechanism through which NOS/NO modulate PANC-1 invasiveness. Suspended INV showed enhanced NO production as well as induction of several pro-metastatic, and stemness-related genes. NOS inhibitor, l-NAME, reduced the expression of these pro-metastatic or stemness-related genes, and dampened spheroid formation ability, suggesting that NO can potentially influence pancreatic cancer aggressiveness. Furthermore, xenograft studies with INV and WCC in NSG mouse model revealed a greater ability of INV compared to WCC, to metastasize to the liver and l-NAME diminished the metastatic lesions in mice injected with INV. Overall, data suggest that NO is a key player associated with resistance to radiation and metastasis of pancreatic cancer; and inhibition of NOS demonstrates therapeutic potential as observed in the animal model by specifically targeting the metastatic cells that harbor stem-like features and are potentially responsible for relapse.
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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.