STAT3: A critical transcription activator in angiogenesis

Chen, Zhong; Han, Zhongchao

doi:10.1002/med.20101

Cited by 266 publications

(208 citation statements)

References 101 publications

Supporting

Mentioning

191

Contrasting

Unclassified

Order By: Relevance

“…The reduced VEGF level resulting from Stat3 knockdown was expected because VEGF expression has been shown to be upregulated by Stat3. 31 The downregulation of angiogenesis related factors (CD34 and VEGF) may lead to the suppression of cancer growth, resulting in reduced tumour size.…”

Section: Discussionmentioning

confidence: 99%

Plasmid-based Stat3 siRNA delivered by hydroxyapatite nanoparticles suppresses mouse prostate tumour growth in vivo

Zhu¹,

Guo²,

Li³

et al. 2011

Asian J Androl

View full text Add to dashboard Cite

DNA vector-based Stat3-specific RNA interference (si-Stat3) blocks Stat3 signalling and inhibits prostate tumour growth. However, the antitumour activity depends on the efficient delivery of si-Stat3. The effects on the growth of mouse prostate cancer cells of si-Stat3 delivered by hydroxyapatite were determined in this study. RM-1 tumour blocks were transplanted into C57BL/6 mice. CaCl 2 -modified hydroxyapatite carrying si-Stat3 plasmids were injected into tumours, and tumour growth and histology were determined. The expression levels of Stat3, pTyr-Stat3, Bcl-2, Bax, Caspase3, VEGF and cyclin D1 were measured by western blot analysis. Amounts of apoptosis in cancer cells were analysed with immunohistochemistry and the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) assay. The results showed that hydroxyapatite-delivered si-Stat3 significantly suppressed tumour growth up to 74% (P,0.01). Stat3 expression was dramatically downregulated in the tumours. The immunohistochemistry and TUNEL results showed that si-Stat3-induced apoptosis (up to 42%, P,0.01). The Stat3 downstream genes Bcl-2, VEGF and cyclin D1 were also strongly downregulated in the tumour tissues that also displayed significant increases in Bax expression and Caspase3 activity. These results suggest that hydroxyapatite can be used for the in vivo delivery of plasmid-based siRNAs into tumours.

show abstract

Section: Discussionmentioning

confidence: 99%

Plasmid-based Stat3 siRNA delivered by hydroxyapatite nanoparticles suppresses mouse prostate tumour growth in vivo

Zhu¹,

Guo²,

Li³

et al. 2011

Asian J Androl

View full text Add to dashboard Cite

show abstract

“…12) Platt et al, 2005). STAT3 has been implicated in the stimulation of angiogenesis by inducing VEGF expression (for review, see Chen and Han, 2007). In addition, VEGF induces activation of STAT3 and promotes its autocrine expression in RECs (Bartoli et al, 2000;Bartoli et al, 2003).…”

Section: Transcriptional Regulation Of Vegf Expression-tissuementioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

636

527

View full text Add to dashboard Cite

Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

show abstract

“…Those gastric cancer cells (6 Â 10 3 cells per well) were directly treated with nitidine chloride (5,10,20,40, and 60 mmol/L) for consecutive 48 hours measured by MTS assay (22). Three independent experiments with triplicate were carried out.…”

Section: Cell Viability Assaymentioning

confidence: 99%

Inhibition of STAT3 Signaling Pathway by Nitidine Chloride Suppressed the Angiogenesis and Growth of Human Gastric Cancer

Chen

Wang

Lin

et al. 2012

Molecular Cancer Therapeutics

139

122

View full text Add to dashboard Cite

STAT3 has been strongly implicated in human malignancies, and constitutive activation of STAT3 serves a crucial role in cell survival, angiogenesis, immune evasion, and inflammation. In this study, we showed that nitidine chloride, a natural phytochemical alkaloid derived from Zanthoxylum nitidum (Roxb) DC, exerts potent anticancer activity through STAT3 signaling cascade. Nitidine chloride dose dependently suppressed VEGFinduced endothelial cell proliferation, migration, and tubular structure formation in vitro and dramatically reduced VEGF-triggered neovascularization in mouse cornea and Matrigel plugs in vivo. This angiogenesis inhibition mediated by nitidine chloride was well interpreted by the suppression of Janus kinase 2/STAT3 signaling and STAT3 DNA-binding activity in endothelial cells. Furthermore, nitidine chloride suppressed the constitutively activated STAT3 protein, its DNA-binding activity, and the expression of STAT3-dependent target genes, including cyclin D1, Bcl-xL, and VEGF in human gastric cancer cells. Consistent with the earlier findings, nitidine chloride inhibited gastric tumor cell growth and induced tumor cell apoptosis in vitro and effectively suppressed the volume, weight, and microvessel density of human SGC-7901 gastric solid tumors (n ¼ 8) at a dosage of 7 mg/kg/d (intraperitoneal injection). Immunohistochemistry and Western blot analysis further revealed that the expression of STAT3, CD31, and VEGF protein in xenografts was remarkably decreased by the alkaloid. Taken together, we propose that nitidine chloride is a promising anticancer drug candidate as a potent STAT3 signaling inhibitor. Mol Cancer Ther; 11(2); 277-87. Ó2011 AACR.

show abstract

STAT3: A critical transcription activator in angiogenesis

Cited by 266 publications

References 101 publications

Plasmid-based Stat3 siRNA delivered by hydroxyapatite nanoparticles suppresses mouse prostate tumour growth in vivo

Plasmid-based Stat3 siRNA delivered by hydroxyapatite nanoparticles suppresses mouse prostate tumour growth in vivo

Vascular endothelial growth factor in eye disease

Inhibition of STAT3 Signaling Pathway by Nitidine Chloride Suppressed the Angiogenesis and Growth of Human Gastric Cancer

Contact Info

Product

Resources

About