ArticleThe American journal of pathology2010
Morphine suppresses tumor angiogenesis through a HIF-1alpha/p38MAPK pathway.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
70 citing papers in PubMed, 3 syntheses or guidelines pooled it, 124 citations in OpenAlex.
- Opioid use and the risk of cancer incidence and mortality: a systematic review.Cancer metastasis reviews · 2025Pooled it
- The organ-specific modulation of malignant processes by opioids: a systematic review of cell culture studies.British journal of cancer · 2025Pooled it
- The effect of anesthetic technique on survival in human cancers: a meta-analysis of retrospective and prospective studies.PloS one · 2013Pooled it
- Antitumor effects of morphine and tramadol on lung metastasis of melanoma tumor cells in vitro and in vivo.Medical oncology (Northwood, London, England) · 2025Article
- Research progress on the impact of opioids on the tumor immune microenvironment (Review).Molecular and clinical oncology · 2025Review
- Knockdown of EBP1 promotes doxorubicin-induced apoptosis in renal clear cell carcinoma cells through activation of the p38/HIF-1α pathway.Oncology letters · 2025Article
- Reduced Taurine Synthesis Underlies Morphine-Promoted Lung Metastasis of Triple-Negative Breast Cancer.Cancers · 2025Article
- The Impact of Potent Addictive Substances on Angiogenic Behavior: A Comprehensive Review.Current neuropharmacology · 2025Review
- The Comparative Effect of Morphine on Proliferation of Cancer Cell Lines Originating from Different Organs: An In Vitro Study.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Influence of Immunoexpression of Mismatch Repair Complex Proteins on Disease-Free Survival in Non-Surgically Treated Oropharyngeal Squamous Cell Carcinomas.Head and neck pathology · 2024Article
- Bidirectional effects of morphine on pancreatic cancer progression via the p38/JNK pathway.Scientific reports · 2024Article
- Pain Management in Animals with Oncological Disease: Opioids as Influencers of Immune and Tumor Cellular Balance.Cancers · 2024Review
- Hypoxia-inducible factor upregulation by roxadustat attenuates drug reward by altering brain iron homoeostasis.Signal transduction and targeted therapy · 2023Article
- Article
- Mapping the Evidence for Opioid-Mediated Changes in Malignancy and Chemotherapeutic Efficacy: Protocol for a Scoping Review.JMIR research protocols · 2023Article
- Influence of opioid analgesia type on circulating tumor cells in open colorectal cancer surgery (POACC-1): study protocol for a prospective randomized multicenter controlled trial.BMC anesthesiology · 2023Article
- Review
- Article
- Morphine stimulates cervical cancer cells and alleviates cytotoxicity of chemotherapeutic drugs via opioid receptor-dependent and -independent mechanisms.Pharmacology research & perspectives · 2022Article
- Opioids and Vitamin C: Known Interactions and Potential for Redox-Signaling Crosstalk.Antioxidants (Basel, Switzerland) · 2022Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Morphine, a highly potent analgesic agent, is frequently prescribed for moderate to severe cancer pain. In this study, morphine was administered at a clinically relevant analgesic dose to assess tumor cell-induced angiogenesis and subcutaneous tumor growth in nude mice using mouse Lewis lung carcinoma cells (LLCs). Implantation of mice with a continuous slow-release morphine pellet achieved morphine plasma levels within 250-400 ng/ml (measured using a radioimmunoassay, Coat-A-Count Serum Morphine) and was sufficient to significantly reduce tumor cell-induced angiogenesis and tumor growth when compared with placebo treatment. Morphometric analysis for blood vessel formation further confirmed that morphine significantly reduced blood vessel density (P < 0.003), vessel branching (P < 0.05), and vessel length (P < 0.002) when compared with placebo treatment. Morphine's effect was abolished in mice coadministered the classical opioid receptor antagonist, naltrexone, and in mu-opioid receptor knockout mice, supporting the involvement of the classical opioid receptors in vivo. Morphine's inhibitory effect is mediated through the suppression of the hypoxia-induced mitochondrial p38 mitogen-activated protein kinase (MAPK) pathway. Our results suggest that in vitro morphine treatment of LLCs inhibits the hypoxia-induced nuclear translocation of hypoxia-inducible transcription factor 1alpha to reduce vascular endothelial growth factor transcription and secretion, in a manner similar to pharmacological blockade with the p38 MAPK-specific inhibitor, SB203585. These studies indicate that morphine, in addition to its analgesic function, may be exploited for its antiangiogenic potential.
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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.