ArticleJournal of gastrointestinal oncology2021
Morphine promotes angiogenesis by activating PI3K/Akt/HIF-1α pathway and upregulating VEGF in hepatocellular carcinoma.
Article in Journal of gastrointestinal oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Inflammatory Signal Persistence in Pain: Lymphatic Regulation and Neuroimmune Integration.Biology · 2026Review
- The HIF-Mediated PI3K-AKT Signaling Pathway Is a Key Signaling Pathway Triggering Testicular Spermatogenic Disorders in Yaks with Cryptorchidism.Veterinary sciences · 2026Article
- Mechanism of Platelet-Rich Plasma in Promoting Diabetic Wound Healing via the PI3K/AKT Signaling Pathway to Regulate Collagen Synthesis and Angiogenesis.Journal of diabetes research · 2026Article
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- Amphiphilic lipid-peptide engineered placenta-derived mesenchymal stem cells for liver fibrosis treatment.Asian journal of pharmaceutical sciences · 2025Article
- Role of Central Inflammatory and Oxidative Pathways in the Morphine Exacerbation of Cardiovascular Effects of Sepsis in Rats.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The Impact of Potent Addictive Substances on Angiogenic Behavior: A Comprehensive Review.Current neuropharmacology · 2025Review
- Narirutin treatment accelerates the process of diabetic wound repair by regulating phenotype switching of macrophages through affecting metabolic reprogramming.Frontiers in pharmacology · 2025Article
- Mechanism of the Traditional Chinese Medicine Simiao Biejia Decoction Improves the Diabetes Mellitus-Induced Erectile Dysfunction in Rats.Drug design, development and therapy · 2025Article
- Hypoxia upregulates hepatic angiopoietin-2 transcription to promote the progression of hepatocellular carcinoma.World journal of hepatology · 2024Article
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- Transthyretin-Regulated Diabetic Retinopathy Through the VEGFA/PI3K/AKT Pathway.Investigative ophthalmology & visual science · 2024Article
- Hypoxia-inducible factor upregulation by roxadustat attenuates drug reward by altering brain iron homoeostasis.Signal transduction and targeted therapy · 2023Article
- Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome.Signal transduction and targeted therapy · 2023Review
- Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies.Frontiers in pharmacology · 2023Review
- Voltage-gated sodium channels: from roles and mechanisms in the metastatic cell behavior to clinical potential as therapeutic targets.Frontiers in pharmacology · 2023Review
- The expression characteristics and clinical significance of ACP6, a potential target of nitidine chloride, in hepatocellular carcinoma.BMC cancer · 2022Article
- Opioids and Vitamin C: Known Interactions and Potential for Redox-Signaling Crosstalk.Antioxidants (Basel, Switzerland) · 2022Review
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Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatocellular carcinoma (HCC) is characterized by the neo-angiogenesis induced by tumor and adjacent cells. It is a leading cancer-related cause of death. Morphine has effects on angiogenesis with pro-angiogenic or anti-angiogenic phonotypes. This study explores the function of morphine on cancer cell growth, angiogenesis and the underlying mechanism in HCC.
methodsMorphine was used to treat BEL-7402 or HCC-LM3 cells and human umbilical vein endothelial cells (HUVECs) were subsequently incubated in the conditioned media (CM) of HCC cells. The potential effects of cell proliferation, migration and tube formation of CM-treated HUVECs were investigated. Furthermore, the angiogenesis regulated factors of VEGFA, PIGF, ANG-1, ANG-2, FGF-1 and FGF-2 were assessed. siRNA and LY294002 were further used to explore the mechanism mediating the effects of morphine on the angiogenesis pathway. The neovascularization effect by morphine was confirmed through the use of human HCC cancer heterotopic mouse model
resultsA significantly increased cell proliferation, migration, and tube formation effect of HUVECs induced by the CM from HCC cell lines treated with morphine was observed. More VEGFA secretion in CM from LM3 or BEL-7402 cell lines was found than the controls (P=0.03 and P=0.027, respectively). VEGFA knock-down could significantly reverse cell proliferation, migration and tube formation induced by the CM from HCC cell lines with morphine treatment. Further molecular experiments indicated that VEGFA secretion was activated by morphine potentially through the PI3K/Akt/HIF-1α pathway. Morphine-induced neovascularization was also observed by the IHC of CD31 and VEGFA.
conclusionsMorphine promotes angiogenesis in hepatocellular carcinoma possibly through the activation of the PI3K/Akt/HIF-1α pathway and VEGFA stimulation.
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