HIF-1α and VEGF are Associated with Disease Progression in Esophageal Carcinoma

Takala, Heikki; Saarnio, Juha; Wiik, Heikki; Ohtonen, Pasi; Soini, Ylermi

doi:10.1016/j.jss.2009.11.725

Cited by 28 publications

(29 citation statements)

References 43 publications

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“…Hypoxia‐inducible genes regulate several biological processes, including cell proliferation, angiogenesis, metabolism, apoptosis, immortalization, and migration 18 . It has been demonstrated that HIF‐1 alpha is associated with invasion and distant metastases 19 . Our observation was further confirmed by wound‐healing and cell invasion assay.…”

Section: Discussionsupporting

confidence: 64%

Hypoxia suppresses E-cadherin and enhances matrix metalloproteinase-2 expression favoring esophageal carcinoma migration and invasion via hypoxia inducible factor-1 alpha activation

Shao

Wang

Chen

et al. 2012

Diseases of the Esophagus

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The goal of this study was to explore the molecular mechanism of hypoxia inducible factor-1 alpha (HIF-1 alpha) action on migration and invasion of esophageal carcinoma cells. We used cobalt chloride (CoCl(2) ) to mimic tumor hypoxic microenvironment and analyzed the expressions of E-cadherin, matrix metalloproteinase-2 (MMP-2), and HIF-1 alpha in esophageal carcinoma cells under hypoxia by reverse transcription polymerase chain reaction and Western blotting. To analyze the function of HIF-1 alpha in Eca109 and TE1 cells, we established stable HIF-1 alpha knockdown cells using small interfering RNA. Blocking effect was detected by Western blotting. The concentrations of MMP-2 protein in the conditioned medium were also determined by enzyme-linked immunosorbent assay. Wound-healing and cell invasion assay were used to evaluate the migration and invasion of esophageal carcinoma cells. After exposure to hypoxia, expressions of HIF-1 alpha protein in Eca109 and TE1 cells were upregulated, both mRNA and protein levels of E-cadherin were downregulated, and MMP-2 were upregulated (P < 0.05), whereas HIF-1 alpha mRNA had no significant change (P > 0.05). Small interfering RNA could block HIF-1 alpha effectively under hypoxia, then enhanced E-cadherin expression and inhibited MMP-2 expression, respectively. Furthermore, expression of HIF-1 alpha protein was stable even though MMP-2 repressed by BB2516. Compared with that in normoxia, Snail expression was enhanced when Eca109 or TE1 cells exposed to hypoxia. Once HIF-1 alpha blocked, Snail expressions were inhibited accordingly. Wound recovery and the number of invading cells decreased (P < 0.05) after HIF-1 alpha blocked. The hypoxia suppresses E-cadherin expression and enhances MMP-2 expression favoring esophageal carcinoma migration and invasion via HIF-1 alpha activation. Our observations suggest that HIF-1 alpha inhibition might be an effective strategy to weaken the migration and invasion of esophageal carcinoma cells.

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Section: Discussionsupporting

confidence: 64%

Hypoxia suppresses E-cadherin and enhances matrix metalloproteinase-2 expression favoring esophageal carcinoma migration and invasion via hypoxia inducible factor-1 alpha activation

Shao

Wang

Chen

et al. 2012

Diseases of the Esophagus

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“…This process is required for the growth of normal and tumor tissues such as esophageal carcinomas (34). Consistent with in vitro and in vivo results from the present study, EGCG has been shown to inhibit tumor growth by downregulating VEGF expression (35,36).…”

Section: Discussionsupporting

confidence: 91%

Molecular mechanism of epigallocatechin-3-gallate in human esophageal squamous cell carcinoma in vitro and in vivo

Liu

Hou

et al. 2014

Oncology Reports

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Abstract. Epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, has been shown to inhibit proliferation in various types of tumors. However, few studies concerning the role and mechanism of EGCG in esophageal squamous cell carcinoma are available. Therefore, the antitumor mechanism of EGCG needs to be investigated. The present study aimed to examine the antitumor effect of EGCG on the human esophageal squamous cell carcinoma cell lines, Eca-109 and Te-1, in vitro and in vivo. Cell viability was assessed using the MTT assay and tumor formation and growth in murine xenograft models with or without EGCG treatment. Cell cycle analysis and levels of reactive oxygen species (ROS) were detected using flow cytometry. Apoptosis was measured by Annexin/propidium iodide staining. Caspase-3 cleavage and vascular endothelial growth factor (VEGF) expression were detected using western blot analysis and immunohistochemistry in tumor cell lines and tumor xenografts, respectively. The results showed that EGCG inhibited proliferation in the Eca-109 and Te-1 cells in a time-and dose-dependent manner. Tumor cells were arrested in the G 1 phase and apoptosis was accompanied by ROS production and caspase-3 cleavage. In a mouse model, EGCG significantly inhibited the growth of Eca-109 tumors by increasing the expression of cleaved-caspase-3 and decreasing VEGF protein levels. Taken together, the results suggest that EGCG inhibits proliferation and induces apoptosis through ROS production, caspase-3 activation, and a decrease in VEGF expression in vitro and in vivo. Furthermore, EGCG may have future clinical applications for novel approaches to treat esophageal squamous cell carcinoma.

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“…(Katušic and Vanhoutte 1986;Rubanyi and Vanhoutte 1986 a,b;Rubanyi 1988;Yanagishawa et al 1988;Lüscher et al 1992). It participates and plays a substantial role in the generation of various diseases like atherosclerosis (Ross 1993(Ross , 1999Heitzer et al 1996;Besler et al 2008;Heistad 2008), essential hypertension (Lüscher 1988;Vanhoutte 1992;Taddei et al 1995;Besler et al 2008), diabetes mellitus and diabetic vasculopathies (Makimattila et al 1996;Bakker et al 2009;Nathanson and Nyström 2009), chronic obstructive pulmonary disease -COPD (Peinado et al 2008), rheumatoid arthritis (Hansel et al 2003;Szekanecz and Koch 2008), psoriatic arthritis (Gonzalez-Juanatey et al 2007), osteoarthritis (Miller et al 2007), ankylosing spondylitis (Sari et al 2006), systemic lupus erythematosus (Piper et al 2007), cancer metastasis (Johansson et al 2010;Takala et al 2010), migraine and stroke (Besler et al 2008;Elliott 2008), anaphylactic and traumatic shock (Menardi et al 2006;Shi et al 2007;Nakashidze 2009), systemic inflammatory response syndrome (Neary and Redmond 1999;Hingorani et al 2000;Menardi et al 2006), NO-induced vasoplegia in sepsis (Stawicki et al 2008;Funk et al 2009) and cardiac surgery …”

Section: The Endotheliummentioning

confidence: 99%

Nitric oxide – the endothelium-derived relaxing factor and its role in endothelial functions

Bauer¹,

Sotníková²

2010

gpb

133

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Abstract. Vascular endothelium plays a key role in the local regulation of vascular tone and vascular architecture by release of vasodilator and vasoconstrictor substances, as well as factors with pro-coagulant, anticoagulant, fibrinolytic, antibacterial properties, growth factors, chemokines, free radicals, etc. Release of endothelium-derived relaxing factors such as nitric oxide (NO), prostaglandins and endothelium-derived hyperpolarizing factor, as well as vasoconstricting factors such as endothelin, superoxide and thromboxanes play an influential role in the maintenance and regulation of vascular tone and the corresponding peripheral vascular resistance. Under physiological conditions, the release of anticoagulant and smooth muscle relaxing factors exceeds the release of other substances. The first part of this review presents the functions of the endothelium itself, the nature of the endothelium-derived relaxing factor, its production by NO synthases, mechanisms of its action via activation of soluble guanylyl cyclase and production of cyclic 3'-5'-guanosine monophosphate. The resulting biological effects include vasodilatation, regulation of vessel wall structure, increased regional blood perfusion, lowering of systemic blood pressure, antithrombosis and antiatherosclerosis effects, which counteract the vascular actions of endogenous vasoconstrictor substances. Impaired endothelial function, either as a consequence of reduced production/release or increased inactivation of endothelium-derived vasodilators, as well as interactions of NO with angiotensin, reactive oxygen species and oxidized lipoproteins, has detrimental functional consequences and is one of the most important cardiovascular risk factors. Therefore the second part of this review assesses the pathophysiologic impact of the endothelium in examples of cardiovascular pathologies, e.g. endotheliopathies caused by increased angiotensin production, lipid peroxidation, ischemia/reperfusion or diabetes.

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HIF-1α and VEGF are Associated with Disease Progression in Esophageal Carcinoma

Cited by 28 publications

References 43 publications

Hypoxia suppresses E-cadherin and enhances matrix metalloproteinase-2 expression favoring esophageal carcinoma migration and invasion via hypoxia inducible factor-1 alpha activation

Hypoxia suppresses E-cadherin and enhances matrix metalloproteinase-2 expression favoring esophageal carcinoma migration and invasion via hypoxia inducible factor-1 alpha activation

Molecular mechanism of epigallocatechin-3-gallate in human esophageal squamous cell carcinoma in vitro and in vivo

Nitric oxide – the endothelium-derived relaxing factor and its role in endothelial functions

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