Fentanyl stimulates tumor angiogenesis via activating multiple pro-angiogenic signaling pathways

Liu, Weiwei; Chen, Yi; Xu, Wei; Wang, Wei; Tang, Li; Xia, Rui

doi:10.1016/j.bbrc.2020.08.038

Cited by 11 publications

(7 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We next showed that oxycodone at the same concentration range also displayed pro-angiogenic activity, but was less potent than morphine. Fentanyl at 0.1 μM to 10 μM stimulates angiogenesis, which is supported by the recent study [ 15 ]. In addition, our findings further extend the previous study that fentanyl at higher concentrations (eg, 100 μM and 1000 μM) gradually lost its stimulatory activity.…”

Section: Discussionsupporting

confidence: 78%

“…In contrast, morphine and fentanyl demonstrate potent pro-angiogenic activities, and oxycodone demonstrates moderate pro-angiogenic activities. Using in vitro angiogenesis models, we and others consistently demonstrate the pro-angiogenetic effects of morphine and fentanyl [ 15 , 28 ]. It is worthy of confirming the effects of opioids on angiogenesis in vivo.…”

Section: Discussionmentioning

confidence: 89%

“…MAPK is activated by receptor tyrosine kinases, G protein–coupled receptors and ion channels [ 33 ], which might be the upstream target of morphine. A recent work reveals that fentanyl simulates angiogenesis via promoting VEGFR2/FAK/PI3K/Akt pathway and increasing activities of small GTPases [ 15 ]. We speculate that VEGFR2-mediated signaling might be involved in fentanyl’s action.…”

Section: Discussionmentioning

confidence: 99%

“…One study demonstrates that fentanyl stimulates angiogenesis in diabetic rats and promotes wound healing [ 14 ]. Another recent study using cell models reveals that fentanyl stimulates tumor angiogenesis [ 15 ]. The effects of oxycodone and codeine in angiogenesis are unknown.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Comparative analysis of the effects of opioids in angiogenesis

et al. 2021

View full text Add to dashboard Cite

Background Angiogenesis, the formation of blood vessel from pre-existing ones, plays an important role in many pathophysiological diseases, such as cancer. Opioids are often used in clinic for the management of chronic pain in cancer patients at terminal phases. Here, we investigated and compared the effects and mechanisms of four opioids on angiogenesis. Methods We performed angiogenesis assays on human umbilical vein endothelial cells (HUVEC) that represent an in vitro model to assess the toxicity of drugs to endothelium. Results Morphine and oxycodone at 0.1 μM to 100 μM dose-dependently increased endothelial cell tube formation and proliferation. We observed the same in endothelial cells exposed to fentanyl at 0.1 μM to 10 μM but there was a gradual loss of stimulation by fentanyl at 100 μM and 1000 μM. Morphine and fentanyl reduced endothelial cell apoptosis-induced by serum withdrawal whereas oxycodone did not display anti-apoptotic effect, via decreasing Bax level. Oxycodone at the same concentrations was less potent than morphine and fentanyl. Different from other three opioids, codeine at all tested concentrations did not affect endothelial cell tube formation, proliferation and survival. Mechanism studies demonstrated that opioids acted on endothelial cells via μ-opioid receptor-independent pathway. Although we observed the increased phosphorylation of mitogen-activated protein kinase (MAPK) in cells exposed to morphine, fentanyl and oxycodone, the rescue studies demonstrated that the stimulatory effects of morphine but not fentanyl nor oxycodone were reversed by a specific MAPK inhibitor. Conclusion Our work demonstrates the differential effects and mechanisms of opioids on angiogenesis.

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Comparative analysis of the effects of opioids in angiogenesis

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Fentanyl inhibits the progression, invasion, and migration of gastric cancer cells by suppressing activity of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/matrix metalloprotoneinase-9 signaling pathway [ 54 ]. Fentanyl also stimulates tumor angiogenesis and promotes the migration of some but not all tested human lung cancer cells; this may be related to the activation of multiple pro-angiogenic signaling pathways, including vascular endothelial growth factor receptor 2/focal adhesion kinase/PI3K/Akt and small guanosine triphosphatases [ 55 ]. This study indicates that fentanyl use in cancer patients may have potential adverse effects and should be administered with caution.…”

Section: Unique Pharmacology Of Fentanyl Treatmentmentioning

confidence: 99%

Unique Pharmacology, Brain Dysfunction, and Therapeutic Advancements for Fentanyl Misuse and Abuse

et al. 2022

View full text Add to dashboard Cite

Fentanyl is a fully synthetic opioid with analgesic and anesthetic properties. It has become a primary driver of the deadliest opioid crisis in the United States and elsewhere, consequently imposing devastating social, economic, and health burdens worldwide. However, the neural mechanisms that underlie the behavioral effects of fentanyl and its analogs are largely unknown, and approaches to prevent fentanyl abuse and fentanyl-related overdose deaths are scarce. This review presents the abuse potential and unique pharmacology of fentanyl and elucidates its potential mechanisms of action, including neural circuit dysfunction and neuroinflammation. We discuss recent progress in the development of pharmacological interventions, anti-fentanyl vaccines, anti-fentanyl/heroin conjugate vaccines, and monoclonal antibodies to attenuate fentanyl-seeking and prevent fentanyl-induced respiratory depression. However, translational studies and clinical trials are still lacking. Considering the present opioid crisis, the development of effective pharmacological and immunological strategies to prevent fentanyl abuse and overdose are urgently needed.

show abstract

LncRNAs associated with vascular mimicry establish a novel molecular subtype and prognostic model for pancreatic cancer

Zhang

Tang

et al. 2023

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

Fentanyl stimulates tumor angiogenesis via activating multiple pro-angiogenic signaling pathways

Cited by 11 publications

References 29 publications

Comparative analysis of the effects of opioids in angiogenesis

Comparative analysis of the effects of opioids in angiogenesis

Unique Pharmacology, Brain Dysfunction, and Therapeutic Advancements for Fentanyl Misuse and Abuse

LncRNAs associated with vascular mimicry establish a novel molecular subtype and prognostic model for pancreatic cancer

Contact Info

Product

Resources

About