SU5416 inhibited VEGF and HIF-1α expression through the PI3K/AKT/p70S6K1 signaling pathway

Zhong, Xiaosong; Zheng, Jenny Z.; Reed, Eddie; Jiang, Bing-Hua

doi:10.1016/j.bbrc.2004.09.082

Cited by 55 publications

(40 citation statements)

References 42 publications

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“…We postulate that this effect was mediated by imatinib through inhibition of the PI3K-Akt and MAPK pathways. [53][54][55] Along the same lines, a recent report demonstrated that imatinib decreased expression of VEGF in lung cancer xenografts. 56 These data support the concept that PDGFR inhibition alters expression of VEGF, suggesting that such agents may modulate tumor growth and survival through indirect effects on angiogenesis and stroma remodeling.…”

Section: Discussionmentioning

confidence: 99%

PDGF BB induces VEGF secretion in ovarian cancer

Matei¹,

Kelich²,

Cao³

et al. 2007

Cancer Biology & Therapy

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Section: Discussionmentioning

confidence: 99%

PDGF BB induces VEGF secretion in ovarian cancer

Matei¹,

Kelich²,

Cao³

et al. 2007

Cancer Biology & Therapy

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“…SU-5416 has been shown to affect PDGF receptor autophosphorylation, but it remains unclear whether SU-5416 impacts the activity of PDGF receptors in intact cells and tissues (10,29). In addition to the hormone receptor effects, SU-5416 does potentially have a number of additional effects including inhibiting the expression of VEGF, hypoxia-inducible factor-1␣, and cyclooxygenase-2 (20,28,37). The contribution of these additional effects of SU-5416 was not specifically evaluated in the present in vivo studies.…”

Section: Discussionmentioning

confidence: 99%

VEGF receptor inhibition blocks liver cyst growth in pkd2(WS25/−) mice

Amura

Brodsky²,

Groff³

et al. 2007

American Journal of Physiology-Cell Physiology

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Proliferation of cyst-lining epithelial cells is an integral part of autosomal dominant polycystic kidney disease (ADPKD) cyst growth. Cytokines and growth factors within cyst fluids are positioned to induce cyst growth. Vascular endothelial growth factor (VEGF) is a pleiotropic growth factor present in ADPKD liver cyst fluids (human 1,128 ± 78, mouse 2,787 ± 136 pg/ml) and, to a lesser extent, in ADPKD renal cyst fluids (human 294 ± 41, mouse 191 ± 90 pg/ml). Western blotting showed that receptors for VEGF (VEGFR1 and VEGFR2) were present in both normal mouse bile ducts and pkd2(WS25/−) liver cyst epithelial cells. Treatment of pkd2(WS25/−) liver cyst epithelial cells with VEGF (50–50,000 pg/ml) or liver cyst fluid induced a proliferative response. The effect on proliferation of liver cyst fluid was inhibited by SU-5416, a potent VEGF receptor inhibitor. Treatment of pkd2(WS25/−) mice between 4 and 8 mo of age with SU-5416 markedly reduced the cyst volume density of the liver (vehicle 9.9 ± 4.3%, SU-5416 1.8 ± 0.7% of liver). SU-5416 treatment between 4 and 12 mo of age markedly protected against increases in liver weight [pkd2(+/+) 4.8 ± 0.2%, pkd2(WS25/−)-vehicle 10.8 ± 1.9%, pkd2(WS25/−)-SU-5416 4.8 ± 0.4% body wt]. The capacity of VEGF signaling to induce in vitro proliferation of pkd2(WS25/−) liver cyst epithelial cells and inhibition of in vivo VEGF signaling to retard liver cyst growth in pkd2(WS25/−) mice indicates that the VEGF signaling pathway is a potentially important therapeutic target in the treatment of ADPKD liver cyst disease.

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“…Previous studies have demonstrated that VEGF receptor inhibitors induce VEGF activity in a murine model of asthma 23,24 and in cancer cell lines under normoxic conditions. 25 From many studies, sorafenib was developed as a receptor tyrosine kinase inhibitor and was approved by the United States Food and Drug Administration in 2005. It has been studied as a multi-kinase inhibitor that targets not only VEGF receptor tyrosine kinase but also other kinases such as Raf serine/threonine kinase.…”

Section: Discussionmentioning

confidence: 99%

Silver nanoparticles modify VEGF signaling pathway and mucus hypersecretion in allergic airway inflammation

Jang¹,

Park²,

Rim³

et al. 2012

IJN

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Abstract:The anti-inflammatory action of silver nanoparticles (NPs) has been reported in a murine model of asthma in a previous study. But more specific mechanisms of silver NPs in an attenuation of allergic airway inflammation have not yet been established. Vascular and mucous changes are believed to contribute largely in pathophysiology in asthma. Among various factors related to vascular changes, vascular endothelial growth factor (VEGF) plays a pivotal role in vascular changes in asthma. Mucin proteins MUC5AC and MUC5B have been implicated as markers of goblet cell metaplasia in lung pathologies. The aim of this study was to investigate the effects of silver NPs on VEGF signaling pathways and mucus hypersecretion. Ovalbumin (OVA)-inhaled female BALBc mice were used to evaluate the role of silver NPs and the related molecular mechanisms in allergic airway disease. In this study, with an OVA-induced murine model of allergic airway disease, it was found that the increased levels of hypoxia-inducible factor (HIF)-1α, VEGF, phosphatidylinositol-3 kinase (PI3K) and phosphorylated-Akt levels, and mucous glycoprotein expression (Muc5ac) in lung tissues were substantially decreased by the administration of silver NPs. In summary, silver NPs substantially suppressed mucus hypersecretion and PI3K/HIF-1α/VEGF signaling pathway in an allergic airway inflammation.

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SU5416 inhibited VEGF and HIF-1α expression through the PI3K/AKT/p70S6K1 signaling pathway

Cited by 55 publications

References 42 publications

PDGF BB induces VEGF secretion in ovarian cancer

PDGF BB induces VEGF secretion in ovarian cancer

VEGF receptor inhibition blocks liver cyst growth in pkd2(WS25/−) mice

Silver nanoparticles modify VEGF signaling pathway and mucus hypersecretion in allergic airway inflammation

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