siRNA targeting VEGF inhibits hepatocellular carcinoma growth and tumor angiogenesis in vivo

Raskopf, E.; Vogt, Annabelle; Sauerbruch, Tilman; Schmitz, Volker

doi:10.1016/j.jhep.2008.07.022

Cited by 71 publications

(70 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[29][30][31][32] It has also been demonstrated that TSP1 can mediate tumor growth suppression via blocking angiogenesis, consistent with our results. 33,34 As previously mentioned HuR has been described to stabilize TSP1 and VEGF mRNA resulting in greater levels and increased protein expression.…”

Section: Discussionsupporting

confidence: 92%

Overexpression of the RNA binding protein HuR impairs tumor growth in triple negative breast cancer associated with deficient angiogenesis

et al. 2010

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 92%

Overexpression of the RNA binding protein HuR impairs tumor growth in triple negative breast cancer associated with deficient angiogenesis

et al. 2010

View full text Add to dashboard Cite

“…Small-interfering RNA transfection MHCC97H cells (1x10 5 ) were seeded into 6-well plates and were grown until 60%-80% confluent. The cells were transiently transfected with 25 nM of SOCS3 small-interfering RNA (siRNA) or negative control siRNA (NC siRNA) using DharmaFECT 4 transfection reagents according to the manufacturer's instructions.…”

Section: Cell Culturementioning

confidence: 99%

“…It has also been reported that overexpression of VEGF exerted a marked increase in HCC development accompanied by augmentation of neovascularization. Furthermore, VEGF knockdown can be related to reduced endothelial cell proliferation and tube formation in vitro and decreased tumor growth and microvessel density in vivo [5].Tie-2, as identified an angiopoietin-2 (Ang-2) receptor, is absolutely required for normal vascular development, apparently by regulating vascular remodeling and maturation in HCC [6]. Recent data demonstrated that tumorigenicity with neovascularization was suppressed by in vivo gene transfer and a soluble Tie-2 expression in a murine HCC model, suggesting a possible role for Tie-2 expression in the induction of HCC neovascularization and disease progression [7].…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II Induces Angiogenic Factors Production Partly Via AT1/JAK2/STAT3/SOCS3 Signaling Pathway in MHCC97H Cells

Ji¹,

Wang

et al. 2012

Cell Physiol Biochem

View full text Add to dashboard Cite

Angiotensin II (Ang II) has been shown to function as a key role in neovascularization of hepatocellular carcinoma (HCC), but little is known its underlying mechanisms. The aim of this study was to explore the role of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in Ang II-induced HCC angiogenic factors production. Herein, we found that Ang II upregulated angiogenic factors production such as vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) and Tie-2 in MHCC97H cells in a time- and concentration-dependent manner. And VEGF and Ang-2 caused a significant increase in angiogenic tube formation. Especially, Ang II-induced angiogenic tube formation was blunted by VEGF small interfering RNA (siRNA) and Ang-2 siRNA, respectively. The JAK2 inhibitor AG490 partly attenuated the effects of Ang II. Moreover, Ang II- induced JAK2 and STAT3 phosphorylation was significantly suppressed by losartan but not PD123319. Meanwhile, STAT3 phosphorylation and suppressor of cytokine signaling 3 (SOCS3) expression induced by Ang II were evidently impaired by AG490. More importantly, SOCS3 siRNA remarkably reinforced Ang II-induced VEGF, Ang-2 and Tie-2 generation in MHCC97H cells. Taken together, the present study demonstrates that Ang II induces angiogenic factors production partly via AT1/ JAK2/STAT3/SOCS3 signaling pathway in MHCC97H cells. These findings may provide important insights into the potential mechanism with respect to the AT1/ JAK2/ STAT3/SOCS3 signaling pathway associated with Ang II-induced angiogenesis in the pathogenesis of HCC.

show abstract

“…6 RNAi-based approaches are currently being considered as potential new therapeutics to both prevent HCC by treating the underlying liver diseases and to cure established HCC. 7 In animal models of HCC or of precancerous liver diseases, synthetic siRNA-mediated gene silencing targeting hepatitis B 8 or hepatitis C 9 viral RNAs and replication intermediates or endogenous liver proteins including the Fas receptor, 10 vascular endothelial growth factor-A (VEGF-A), 11,12 cell-cycle-activating phosphatase CDC25B, 13 and heme oxygenase 1, 14 has been shown to efficiently reduce target protein expression and inhibit disease progression. Another promising RNAi-based therapeutic strategy consists in the administration of microRNAs, which are down-regulated in HCC.…”

mentioning

confidence: 99%

Small Interfering RNAs Induce Target-Independent Inhibition of Tumor Growth and Vasculature Remodeling in a Mouse Model of Hepatocellular Carcinoma

Bergé

Bonnin

Sulpice

et al. 2010

The American Journal of Pathology

View full text Add to dashboard Cite

RNA interference mediated by small interfering RNAs (siRNAs) has emerged as a potential therapeutic approach to treat various diseases, including cancer. Recent studies with several animal models of posttraumatic revascularization demonstrated that synthetic siRNAs may produce therapeutic effects in a target-independent manner through the stimulation of the toll-like receptor-3 (TLR3)/interferon pathway and suppression of angiogenesis. To analyze the impact of siRNAs on tumor angiogenesis, we injected transgenic mice developing hepatocellular carcinoma (HCC) with either control siRNAs or siRNA targeting neuropilin-1. We found that treatment with these siRNAs led to a comparable reduction in tumor liver volume and to inhibition of tumor vasculature remodeling. We further determined that TLR3, which recognizes double-stranded siRNA, was up-regulated in mouse HCC. Treatment of HCC mice with polyinosinic-polycytidylic acid [poly(I:C)], a TLR3 agonist, led to both a reduction of tumor liver enlargement and a decrease in hepatic arterial blood flow, indicating that TLR3 is functional and may mediate both anti-angiogenic and anti-tumor responses. We also demonstrated that siRNAs increased interferon-␥ levels in the liver. In vitro , interferon-␥ inhibited proliferation of endothelial cells. In addition, we found that siRNAs inhibited endothelial cell proliferation and morphogenesis in an interferon-␥-independent manner. Our results suggest that synthetic siRNAs inhibit target-independently HCC growth and angiogenesis through the activation of the innate interferon response and by directly inhibiting endothelial cell function.

show abstract

siRNA targeting VEGF inhibits hepatocellular carcinoma growth and tumor angiogenesis in vivo

Cited by 71 publications

References 32 publications

Overexpression of the RNA binding protein HuR impairs tumor growth in triple negative breast cancer associated with deficient angiogenesis

Overexpression of the RNA binding protein HuR impairs tumor growth in triple negative breast cancer associated with deficient angiogenesis

Angiotensin II Induces Angiogenic Factors Production Partly Via AT1/JAK2/STAT3/SOCS3 Signaling Pathway in MHCC97H Cells

Small Interfering RNAs Induce Target-Independent Inhibition of Tumor Growth and Vasculature Remodeling in a Mouse Model of Hepatocellular Carcinoma

Contact Info

Product

Resources

About