Effects of α-adrenoreceptor antagonists on apoptosis and proliferation of pancreatic cancer cells in vitro

Shen, Si-Lian; Zhang, Dong; Hu, Hengtong; Li, Junhui; Wang, Zheng; Ma, Qingyong

doi:10.3748/wjg.14.2358

Cited by 38 publications

(26 citation statements)

References 24 publications

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“…Different a2-adrenoceptor agonists have been associated with the induction of apoptosis in a variety of cell types (42,43), including neutrophils (44). Similar concentrations of peripheral blood neutrophils were found in xylazine-treated and control animals (data not shown).…”

Section: A2-adrenoceptorsupporting

confidence: 64%

Prevention of Neutrophil Extravasation by α2-Adrenoceptor–Mediated Endothelial Stabilization

Herrera-García

Domínguez-Luis

Arce-Franco

et al. 2014

The Journal of Immunology

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Adrenergic receptors are expressed on the surface of inflammation-mediating cells, but their potential role in the regulation of the inflammatory response is still poorly understood. The objectives of this work were to study the effects of α2-adrenergic agonists on the inflammatory response in vivo and to determine their mechanism of action. In two mouse models of inflammation, zymosan air pouch and thioglycolate-induced peritonitis models, the i.m. treatment with xylazine or UK14304, two α2-adrenergic agonists, reduced neutrophil migration by 60%. The α2-adrenergic antagonist RX821002 abrogated this effect. In flow cytometry experiments, the basal surface expression of L-selectin and CD11b was modified neither in murine nor in human neutrophils upon α2-agonist treatment. Similar experiments in HUVEC showed that UK14304 prevented the activation-dependent upregulation of ICAM-1. In contrast, UK14304 augmented electrical resistance and reduced macromolecular transport through a confluent HUVEC monolayer. In flow chamber experiments, under postcapillary venule-like flow conditions, the pretreatment of HUVECs, but not neutrophils, with α2-agonists decreased transendothelial migration, without affecting neutrophil rolling. Interestingly, α2-agonists prevented the TNF-α–mediated decrease in expression of the adherens junctional molecules, VE-cadherin, β-catenin, and plakoglobin, and reduced the ICAM-1–mediated phosphorylation of VE-cadherin by immunofluorescence and confocal analysis and Western blot analysis, respectively. These findings indicate that α2-adrenoceptors trigger signals that protect the integrity of endothelial adherens junctions during the inflammatory response, thus pointing at the vascular endothelium as a therapeutic target for the management of inflammatory processes in humans.

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Section: A2-adrenoceptorsupporting

confidence: 64%

Prevention of Neutrophil Extravasation by α2-Adrenoceptor–Mediated Endothelial Stabilization

Herrera-García

Domínguez-Luis

Arce-Franco

et al. 2014

The Journal of Immunology

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“…When under chronic stress, the human sympathetic nervous system keeps releasing catecholamines, such as epinephrine, norepinephrine, dopamine etc. It has been confirmed by in vitro experiments that catecholamine promotes the proliferation and metastasis of cancer of the breast [4], pancreas [5], melanomas [6], esophagus [7,] and colon [8]. Most studies have proven the key role of the β-adrenoreceptor during tumorigenesis.…”

Section: Introductionmentioning

confidence: 74%

Epinephrine Stimulates Cell Proliferation and Induces Chemoresistance in Myeloma Cells through the β-Adrenoreceptor in vitro

Yu¹,

Zhuang²

2017

Acta Haematol

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Objectives: To explore the effect of the β-adrenoreceptor signaling pathway on myeloma cells. Methods: The myeloma U266 cell line was treated with epinephrine and propranolol. Cell proliferation was analyzed by MTS assay. Apoptosis was detected by flow cytometry. The β-receptor subtype and the key enzyme of epinephrine were identified by reverse transcription polymerase chain reaction (RT-PCR). Results: Epinephrine (5-50 μM) promoted U266 cell growth in a dose-dependent manner and neutralized the inhibition effect of bortezomib (25 and 50 ng/mL) in vitro. Cell proliferation was inhibited by a β-receptor antagonist, propranolol, at a concentration of 50-200 μM. The proportions of early and late apoptotic cells were enhanced after treatment with propranolol. The expression of caspase 3/7, 8, and 9 was elevated in propranolol-treated myeloma cells. Both β₁- and β₂-adrenoceptor mRNAs were expressed in the U266 cell line. Key enzymes dopamine hydroxylase and tyrosinehydroxylase were identified in myeloma cells. Conclusions: Our results reveal that epinephrine stimulates myeloma cell growth in vitro while the β-blocker propranolol has an antiproliferative effect, indicating that stress hormones may trigger the progression of myeloma.

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“…All these drugs were obtained from the Sigma Chemical Co (USA). Inhibitor concentrations employed were LY294002 ( siRNA Assay MIA PaCa2 and BxPC-3 cells 2×10 6 were transfected with siRNA targeted against HIF-1α (100 nm/L) or control siRNA (Qiagen) using Lipofectamine 2000 (Invitrogen). Cells were recovered overnight before starvation, followed by treatment with xamoterol (1 μmol/L) or salbutamol (1 μmol/L) for 12 h, and then harvested for real-time PCR.…”

Section: Cell Cultures and Treatmentsmentioning

confidence: 99%

“…A normal pancreatic duct epithelial cell line and several pancreatic cancer cell lines express β1 and/or β2-ARs as well as epidermal growth factor receptor (EGFR) including Panc-1, BXPC-3, PC-2, PC-3, and HPDE6-c7. Moreover, the EGFR is frequently over-expressed in pancreatic cancer [4][5][6] .…”

Section: Introductionmentioning

confidence: 99%

HIF-1α links β-adrenoceptor agonists and pancreatic cancer cells under normoxic condition

Qing

Zhang

et al. 2009

Acta Pharmacol Sin

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Aim: To examine whether β-adrenoceptor (β-AR) agonists can induce hypoxia-inducible factor (HIF)-1α accumulation which then upregulate the expression of its target genes in pancreatic cancer cells at normoxia, and to further elucidate the mechanism involved. Methods: Pulse-chase assay, RT-PCR, and Western blot were employed to detect the effects of β-AR agonists and antagonists, siRNA as well as several inhibitors of signal transduction pathways on MIA PaCa2 and BxPC-3 pancreatic cancer cells. Results: Treatment of pancreatic cancer cell lines with β-AR agonists led to accumulation of HIF-1α and then up-regulated expression of its target genes independently of oxygen levels. The induction was partly or completely inhibited not only by β-AR antagonists but also by inhibitors of PKA transduction pathways and by siHIF-1α. Both β1-AR and β2-AR agonists produced the above-mentioned effects, but β2-AR agonist was more potent. Conclusion: Activation of β-AR receptor transactivates epidermal growth factor receptor (EGFR) and then elicites Akt and ERK1/2 in a PKA-dependent manner, which together up-regulate levels of HIF-1α and downstream target genes independently of oxygen level. Our data suggest a novel mechanism in pancreatic cancer cells that links β-AR and HIF-1α signaling under normoxic conditions, with implications for the control of glucose transport, angiogenesis and metastasis.

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Effects of α-adrenoreceptor antagonists on apoptosis and proliferation of pancreatic cancer cells in vitro

Cited by 38 publications

References 24 publications

Prevention of Neutrophil Extravasation by α2-Adrenoceptor–Mediated Endothelial Stabilization

Prevention of Neutrophil Extravasation by α2-Adrenoceptor–Mediated Endothelial Stabilization

Epinephrine Stimulates Cell Proliferation and Induces Chemoresistance in Myeloma Cells through the β-Adrenoreceptor in vitro

HIF-1α links β-adrenoceptor agonists and pancreatic cancer cells under normoxic condition

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