共查询到20条相似文献,搜索用时 15 毫秒
1.
Afsaneh Sadremomtaz Farzad Kobarfard Kamran Mansouri Laleh Mirzanejad 《Journal of receptor and signal transduction research》2013,33(5-6):432-441
AbstractBackground: Vascular endothelial growth factor (VEGF) A and B are endothelial cell mitogens whose ligation to VEGFR1/VEGFR2 drives tumor angiogenesis and metastasis, and epithelial-mesenchymal transition (EMT). Blockade of these signaling axes could be obtained by disturbing the interactions between VEGFA and/or VEGFB with VEGFR1 and/or VEGFR2.Methods: A 14-mer peptide (VGB) that recognizes both VEGFR1 and VEGFR2 were investigated for its inhibitory effects on the VEGF‐induced proliferation and migration using MTT and scratch assay, respectively. Downstream signaling pathways were also assessed by quantitative estimation of gene and protein expression using real-time PCR and immunohistochemistry (IHC).Results: We investigated the inhibitory effects of VGB on downstream mediators of metastasis, including epithelial-cadherin (E-cadherin), matrix metalloprotease-9 (MMP-9), cancer myelocytomatosis (c-Myc), and nuclear factor-κβ (NF-κβ), and migration, comprising focal adhesion kinase (FAK) and its substrate Paxilin. VGB inhibited the VEGF‐induced proliferation of human umbilical vein endothelial cells (HUVECs), 4T1 and U87 cells in a time- and dose-dependent manner and migration of HUVECs. Based on IHC analyses, treatment of 4T1 mammary carcinoma tumor with VGB led to the suppression of p-AKT, p-ERK1/2, MMP-9, NF-κβ, and activation of E-cadherin compared with PBS-treated controls. Moreover, quantitative real-time PCR analyses of VGB-treated tumors revealed the reduced expression level of FAK, Paxilin, NF-κβ, MMP-9, c-Myc, and increased expression level of E-cadherin compared to PBS-treated controls.Conclusions: Our results demonstrated that simultaneous blockade of VEGFR1/VEGFR2 is an effective strategy to fight solid tumors by targeting a wider range of mediators involved in tumor angiogenesis, growth, and metastasis. 相似文献
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Vascular endothelial growth factor receptor 2 (VEGFR‐2) plays a critical role in tumor angiogenesis. None therapeutic antibodies targeting VEGFR‐2 are available in clinical use. Herein, we describe the screening of a new single‐chain antibody fragment (scFv) targeting extracellular domain 3 of human VEGFR‐2 (kinase insert domain‐containing receptor [KDR]3) from Griffin phage display scFv library. A comprehensive sequence analysis was performed to assign the framework and complementary‐determining regions. The scFv exerted particular binding sites to KDR3 on molecular docking, and the binding affinity was further convinced by binding analysis both in quantitative ELISA and real‐time kinetic determination by biosensors (KD = 40 nM). Finally, the scFv was revealed to inhibit VEGF‐stimulated proliferation of human umbilical vein endothelial cells (HUVECs; IC50 = 5 nM) and to inhibit HUVEC migration significantly at 17 nM. Taken together, our results indicate that we have successfully isolated a scFv which differentially recognizes KDR3 and has potential clinical applications in the treatment of angiogenesis related diseases. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 28: 981–989, 2012 相似文献
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Rui Zeng Xiao-fei Jiang Yu-cheng Chen Yuan-ning Xu Song-hong Ma Zhi Zeng Rui Liu Ou Qiang Xian Li 《Cytotechnology》2014,66(4):655-665
The purpose of this study was to determine the relationship between VEGF and mini-TyrRS/mini-TrpRS in angiogenesis in hypoxic culture and to begin to comprehend their mechanism in angiogenesis. We designed a VEGF gene silencing assay by using lentivirus vectors, and then western blotting was used to determine the protein expression of VEGF, VEGFR2 and pVEGFR2 in three groups in hypoxic culture at 3, 6, 12, or 24 h: (1) untransfected human umbilical vein endothelial cells (HUVECs) (Control); (2) pGCSIL-GFP lentivirus vector-transduced HUVECs (Mock); and (3) pGCSIL-shVEGF lentivirus vector-transduced HUVECs (Experimental). We also detected the effects of mini-TyrRS/mini-TrpRS peptides on HUVEC proliferation, migration and tube formation after lentivirus vector transfection and VEGFR2 antibody injection. The results indicated that expression of the mini-TyrRS protein was increased, whereas that of mini-TrpRS was specifically decreased in hypoxic culture both in control and mock groups. However, this trend in protein levels of mini-TyrRS and mini-TrpRS was lost in the experimental group after transduction with the pGCSIL-shVEGF lentivirus vector. The protein expression of VEGF was increased in hypoxic culture both in control and mock groups. After transduction with the pGCSIL-shVEGF lentivirus vector, the protein level of VEGF was noticeably decreased in the experimental group; however, for VEGFR2, the results showed no significant difference in VEGFR2 protein expression in any of the groups. For pVEGFR2, we found a distinct trend from that seen with VEGF. The protein expression of pVEGFR2 was sharply increased in hypoxic culture in the three groups. The addition of mini-TyrRS significantly promoted proliferation, migration and tube formation of HUVECs, while mini-TrpRS inhibited these processes in both control and mock groups in hypoxic culture. However, these effects disappeared after transduction with the pGCSIL-shVEGF lentivirus vector in the experimental group, but no significant difference was observed after VEGFR2 antibody injection. The protein expression of VEGF is similar to that of mini-TyrRS in hypoxic culture and plays an important role in the mini-TyrRS/mini-TrpRS-stimulated proliferation, migration and tube formation of HUVECs in hypoxia. These results also suggest that the change in mini-TyrRS and mini-TrpRS expression in hypoxic culture is not related to VEGFR2 and that some other possible mechanisms, are involved in the phosphorylation of VEGFR2. 相似文献
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Afsaneh Sadremomtaz Kamran Mansouri Golnaz Alemzadeh Majid Safa Ahmadreza Esmaeili Rastaghi S. Mohsen Asghari 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(12):2688-2700
Background
Neutralization of vascular endothelial growth factor receptor 1 (VEGFR1) and/or VEGFR2 is a widely used means of inhibiting tumor angiogenesis.Methods
Based on the complex X-ray structures of VEGFA/VEGFR1, VEGFA/VEGFR2, and VEGFB/VEGFR1, a peptide (referred to as VGB) was designed to simultaneously bind to VEGFR1 and VEGFR2, and binding, antiangiogenic and antitumor properties of the peptide was investigated in vitro.Results
VGB bound to both VEGFR1 and VEGFR2 in human umbilical vein endothelial cells (HUVECs) and 4?T1 mammary carcinoma tumor (MCT) cells, and inhibited the proliferation of HUVE, 4?T1 MCT, and U87 glioblastoma cells. Through abrogation of AKT and ERK1/2 phosphorylation, VEGFA-stimulated proliferation, migration, and two- and three-dimensional tube formation in HUVECs were inhibited more potently by VGB than by bevacizumab. In a murine 4?T1 MCT model, VGB strongly inhibited tumor growth without causing weight loss, accompanied by inhibition of AKT and ERK1/2 phosphorylation, a significant decrease in tumor cell proliferation (Ki-67 expression), angiogenesis (CD31 and CD34 expression), an increase in apoptosis index (increased TUNEL staining and p53 expression and decreased Bcl-2 expression), and the suppression of systematic spreading of the tumor (reduced NF-κB and MMP-9 and increased E-cadherin expression).Conclusion
The dual specificity of VGB for VEGFR1 and VEGFR2, through which the PI3K/AKT and MAPK/ERK1/2 signaling pathways can be abrogated and, subsequently, angiogenesis, tumor growth, and metastasis are inhibited.General significance
This study demonstrated that simultaneous blockade of VEGFR1 and VEGFR2 downstream cascades is an effective means for treatment of various angiogenic disorders, especially cancer. 相似文献7.
Dongheon Lee Dongin Kim Yu Bin Choi Kyungjae Kang Eun-Sil Sung Jin-Hyung Ahn 《MABS-AUSTIN》2016,8(5):892-904
Several angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) signaling pathway have been approved for cancer treatment. However, VEGF inhibitors alone were shown to promote tumor invasion and metastasis by increasing intratumoral hypoxia in some preclinical and clinical studies. Emerging reports suggest that Delta-like ligand 4 (Dll4) is a promising target of angiogenesis inhibition to augment the effects of VEGF inhibitors. To evaluate the effects of simultaneous blockade against VEGF and Dll4, we developed a bispecific antibody, HD105, targeting VEGF and Dll4. The HD105 bispecific antibody, which is composed of an anti-VEGF antibody (bevacizumab-similar) backbone C-terminally linked with a Dll4-targeting single-chain variable fragment, showed potent binding affinities against VEGF (KD: 1.3 nM) and Dll4 (KD: 30 nM). In addition, the HD105 bispecific antibody competitively inhibited the binding of ligands to their receptors, i.e., VEGF to VEGFR2 (EC50: 2.84 ± 0.41 nM) and Dll4 to Notch1 (EC50: 1.14 ± 0.06 nM). Using in vitro cell-based assays, we found that HD105 effectively blocked both the VEGF/VEGFR2 and Dll4/Notch1 signaling pathways in endothelial cells, resulting in a conspicuous inhibition of endothelial cell proliferation and sprouting. HD105 also suppressed Dll4-induced Notch1-dependent activation of the luciferase gene. In vivo xenograft studies demonstrated that HD105 more efficiently inhibited the tumor progression of human A549 lung and SCH gastric cancers than an anti-VEGF antibody or anti-Dll4 antibody alone. In conclusion, HD105 may be a novel therapeutic bispecific antibody for cancer treatment. 相似文献
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血管内皮生长因子受体信号转导通路与肿瘤血管生成 总被引:2,自引:0,他引:2
血管内皮生长因子是促进血管生成的重要调节因子.它能促进内皮细胞增殖、迁移,阻止内皮细胞凋亡、管腔网状结构退化,增加血管渗透性.所有这些作用都是通过血管内皮生长因子受体信号转导通路实现的.它们在肿瘤血管生成、肿瘤生长中起着重要的作用.以血管内皮生长因子受体信号转导通路为靶点是开发肿瘤血管生成抑制剂的理想策略. 相似文献
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《Journal of receptor and signal transduction research》2013,33(2-3):239-254
AbstractVascular endothelial growth factor receptors (VEGFR) are considered essential for angiogenesis. The VEGFR‐family proteins consist of VEGFR‐1/Flt‐1, VEGFR‐2/KDR/Flk‐1, and VEGFR‐3/Flt‐4. Among these, VEGFR‐2 is thought to be principally responsible for angiogenesis. However, the precise role of VEGFRs1–3 in endothelial cell biology and angiogenesis remains unclear due in part to the lack of VEGFR‐specific inhibitors. We used the newly described, highly selective anilinoquinazoline inhibitor of VEGFR‐2 tyrosine kinase, ZM323881 (5‐[[7‐(benzyloxy) quinazolin‐4‐yl]amino]‐4‐fluoro‐2‐methylphenol), to explore the role of VEGFR‐2 in endothelial cell function. Consistent with its reported effects on VEGFR‐2 [IC(50) < 2 nM], ZM323881 inhibited activation of VEGFR‐2, but not of VEGFR‐1, epidermal growth factor receptor (EGFR), platelet‐derived growth factor receptor (PDGFR), or hepatocyte growth factor (HGF) receptor. We studied the effects of VEGF on human aortic endothelial cells (HAECs), which express VEGFR‐1 and VEGFR‐2, but not VEGFR‐3, in the absence or presence of ZM323881. Inhibition of VEGFR‐2 blocked activation of extracellular regulated‐kinase, p38, Akt, and endothelial nitric oxide synthetase (eNOS) by VEGF, but did not inhibit p38 activation by the VEGFR‐1‐specific ligand, placental growth factor (PlGF). Inhibition of VEGFR‐2 also perturbed VEGF‐induced membrane extension, cell migration, and tube formation by HAECs. Vascular endothelial growth factor receptor‐2 inhibition also reversed VEGF‐stimulated phosphorylation of CrkII and its Src homology 2 (SH2)‐binding protein p130Cas, which are known to play a pivotal role in regulating endothelial cell migration. Inhibition of VEGFR‐2 thus blocked all VEGF‐induced endothelial cellular responses tested, supporting that the catalytic activity of VEGFR‐2 is critical for VEGF signaling and/or that VEGFR‐2 may function in a heterodimer with VEGFR‐1 in human vascular endothelial cells. 相似文献
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《Cell communication & adhesion》2013,20(5):85-103
AbstractVascular Endothelial Growth Factor receptors (VEGFRs), the interactions with their ligands and the subsequent signalling pathways are known to play a vital role in tumour angiogenesis. Initial clinical trials of VEGFR inhibitors were disappointing but over the past decade some therapies have been successfully brought to market. At present, VEGFR inhibitors appear to be most promising as adjuvants to conventional chemotherapy. However, several interacting signalling molecules and downstream pathways have recently been shown to interact with VEGFR signalling and provide promising novel targets, such as the platelet-derived growth factor (PDGF), epithelial growth factor (EGF), human epithelial receptor-2, (HER-2) Tie-2 and oestrogen receptors. Elucidation of this web of signalling pathways may identify new therapeutic strategies which may be used in combination with VEGFR inhibitors to augment the efficacy of anti-angiogenic cancer treatments. This review assesses the role of modulating VEGFR activity in cancer and systematically examines current evidence and trials in this area. 相似文献
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Deepa Alex Emilia Conceição Leong Zai‐Jun Zhang Gloria Tse Ho Yan Shuk‐Han Cheng Chi‐Weng Leong Zhen‐Hua Li Kai‐Heng Lam Shun‐Wan Chan Simon Ming‐Yuen Lee 《Journal of cellular biochemistry》2010,109(2):339-346
Angiogenesis plays an important role in the development of neoplastic diseases such as cancer. Resveratrol and its derivatives exert antiangiogenic effects, but the mechanisms of their actions remain unclear. The aim of this study was to evaluate the antiangiogenic activity of resveratrol and its derivative trans‐3,5,4′‐trimethoxystilbene in vitro using human umbilical vein endothelial cells (HUVECs) and in vivo using transgenic zebrafish, and to clarify their mechanisms of action in zebrafish by gene expression analysis of the vascular endothelial growth factor (VEGF) receptor (VEGFR2/KDR) and cell‐cycle analysis. trans‐3,5,4′‐Trimethoxystilbene showed significantly more potent antiangiogenic activity than that of resveratrol in both assays. In zebrafish, trans‐3,5,4′‐trimethoxystilbene caused intersegmental vessel regression and downregulated VEGFR2 mRNA expression. Trans‐3,5,4′‐trimethoxystilbene also induced G2/M cell‐cycle arrest, most specifically in endothelial cells of zebrafish embryos. We propose that the antiangiogenic and vascular‐targeting activities of trans‐3,5,4′‐trimethoxystilbene result from the downregulation of VEGFR2 expression and cell‐cycle arrest at G2/M phase. J. Cell. Biochem. 109: 339–346, 2010. © 2009 Wiley‐Liss, Inc. 相似文献
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Choi HE Yoo MS Choi JH Lee JY Kim JH Kim JH Lee JK Kim GI Park Y Chi YH Paik SH Lee JH Lee KT 《Bioorganic & medicinal chemistry letters》2011,21(21):6236-6241
Anti-angiogenesis is regarded as an effective strategy for cancer treatment, and vascular endothelial growth factor (VEGF) plays a key role in the regulations of angiogenesis and vasculogenesis. In the present study, the authors synthesized five novel nicotinamide derivatives which structurally mimic the receptor tyrosine kinase inhibitor sunitinib and evaluated their anti-angiogenic effects. Transwell migration assays revealed that 2-(1-benzylpiperidin-4-yl) amino-N-(3-chlorophenyl) nicotinamide (BRN-103), among the five derivatives most potently inhibited VEGF-induced human umbilical vein endothelial cells (HUVECs). In addition, BRN-103 dose-dependently inhibited VEGF-induced migration, proliferation, and capillary-like tube formation of HUVECs and vessel sprouting from mouse aortic rings. To understand the molecular mechanisms responsible for these activities, the authors examined the effect of BRN-103 on VEGF signaling pathways in HUVECs. BRN-103 was found to suppress the VEGF-induced phosphorylation of VEGF receptor 2 (VEGR2) and the activations of AKT and eNOS. Taken together, these results suggest that BRN-103 inhibits VEGF-mediated angiogenesis signaling in human endothelial cells. 相似文献
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Yueshui Zhao Sipeng Guo Jian Deng Jing Shen Fukuan Du Xu Wu Yu Chen Mingxing Li Meijuan Chen Xiaobing Li Wanping Li Li Gu Yuhong Sun Qinglian Wen Jing Li Zhangang Xiao 《International journal of biological sciences》2022,18(9):3845
Non-small cell lung cancer (NSCLC) is the leading cause of death by cancer worldwide. Despite developments in therapeutic approaches for the past few decades, the 5-year survival rate of patients with NSCLC remains low. NSCLC tumor is a complex, heterogeneous microenvironment, comprising blood vessels, cancer cells, immune cells, and stroma cells. Vascular endothelial growth factors (VEGFs) are a major mediator to induce tumor microvasculature and are associated with the progression, recurrence, and metastasis of NSCLC. Current treatment medicines targeting VEGF/VEGF receptor (VEGFR) pathway, including neutralizing antibodies to VEGF or VEGFR and receptor tyrosine kinase inhibitors, have shown good treatment efficacy in patients with NSCLC. VEGF is not only an important angiogenic factor but also an immunomodulator of tumor microenvironment (TME). VEGFs can suppress antigen presentation, stimulate activity of regulatory T (Treg) cells, and tumor-associated macrophages, which in turn promote an immune suppressive microenvironment in NSCLC. The present review focuses on the angiogenic and non-angiogenic functions of VEGF in NSCLC, especially the interaction between VEGF and the cellular components of the TME. Additionally, we discuss recent preclinical and clinical studies to explore VEGF/VEGFR-targeted compounds and immunotherapy as novel approaches targeting the TME for the treatment of NSCLC. 相似文献
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A novel bispecific diabody targeting both vascular endothelial growth factor receptor 2 and epidermal growth factor receptor for enhanced antitumor activity
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Haizhen Jin Zhiguo Chen Wei Xie Youfu Wang Yang Wang Min Wang Juan Zhang Desmond Omane Acheampong 《Biotechnology progress》2016,32(2):294-302
Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 2 (VEGFR2) are receptor tyrosine kinases known to play critical roles in the development and progression of tumors. Based on the cross‐talk between EGFR and VEGFR2 signal pathways, we designed and produced a bispecific diabody (bDAb) targeting both EGFR and VEGFR2 simultaneously. The bispecific molecule (EK‐02) demonstrated that it could bind to HUVEC (VEGFR2 high‐expressing) and A431 (EGFR overexpressing) cells. Additionally, similar to the parental antibodies, it was able to inhibit proliferation and migration, and induced apoptosis in these cells (HUVECs and A431), demonstrating that it had retained the functional properties of its parental antibodies. Furthermore, the efficacy of EK‐02 was evaluated using the human colon adenocarcinoma cell line HT29 (VEGFR2 and EGFR coexpressing). In vitro assay showed that EK‐02 could bind to HT29 cells, restrain cell growth and migration, and induce apoptosis with enhanced efficacy compared to both parental antibodies. Further, it inhibited the neovascularization and tumor formation on an HT29 cell bearing chicken chorioallantoic membrane (CAM) tumor model in vivo. In conclusion, these data suggest that the novel bDAb (EK‐02) has antiangiogenesis and antitumor capacity both in vitro and in vivo, and can possibly be used as cotargeted therapy for the treatment of EGFR and VEGFR2 overexpressing tumors. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:294–302, 2016 相似文献
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Pengfei Yu Qian Liu Kun Liu Kazumi Yagasaki Erxi Wu Guoying Zhang 《Cytotechnology》2009,59(3):219-229
Matrine has shown therapeutic and/or adjuvant therapeutic effects on the treatment of some patients with breast cancer. However,
its mechanisms of action are largely unknown. To disclose the mechanisms, we investigated in vitro and ex vivo effects of
matrine on the cancer cells. Our results confirmed that matrine significantly suppressed the proliferation of highly-metastatic
human breast cancer MDA-MB-231 cell line. Matrine displayed synergistic effects with existing anticancer agents celecoxib
(the inhibitor of cyclooxygenase-2), trichostatin A (the histone deacetylase inhibitor) and rosiglitazone against the proliferation
and VEGF excretions in MDA-MB-231 cells. Matrine induced the apoptosis and cell cycle arrest by reducing the ratios of Bcl-2/Bax
protein and mRNA levels in the cancer cells. Matrine significantly reduced the invasion, MMP-9/MMP-2 activation, Akt phosphorylation,
nuclear factor κB p-65 expression and DNA binding activity, and mRNA levels of MMP-9, MMP-2, EGF and VEGFR1 in MDA-MB-231 cells. Collectively,
our results suggest that matrine inhibits the cancer cell proliferation and invasion via EGF/VEGF-VEGFR1-Akt-NF-κB signaling pathway. 相似文献
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Bufalin, a naturally occurring small-molecule compound from Traditional Chinese Medicine (TCM) Chansu showed inhibitory effects against human prostate, hepatocellular, endometrial and ovarian cancer cells, and leukemia cells.
However, whether or not bufalin has inhibitory activity against the proliferation of human non–small cell lung cancer (NSCLC)
cells is unclear. The aim of this study is to study the effects of bufalin on the proliferation of NSCLC and its molecular
mechanisms of action. The cancer cell proliferation was measured by MTT assay. The apoptosis and cell cycle distribution were
analyzed by flow cytometry. The protein expressions and phosphorylation in the cancer cells were detected by Western blot
analysis. In the present study, we have demonstrated that bufalin suppressed the proliferation of human NSCLC A549 cell line
in time- and dose-dependent manners. Bufalin induced the apoptosis and cell cycle arrest by affecting the protein expressions
of Bcl-2/Bax, cytochrome c, caspase-3, PARP, p53, p21WAF1, cyclinD1, and COX-2 in A549 cells. In addition, bufalin reduced the protein levels of receptor
expressions and/or phosphorylation of VEGFR1, VEGFR2, EGFR and/or c-Met in A549 cells. Furthermore, bufalin inhibited the
protein expressions and phosphorylation of Akt, NF-κB, p44/42 MAPK (ERK1/2) and p38 MAPK in A549 cells. Our results suggest that bufalin inhibits the human lung cancer cell proliferation
via VEGFR1/VEGFR2/EGFR/c-Met–Akt/p44/42/p38-NF-κB signaling pathways; bufalin may have a wide therapeutic and/or adjuvant therapeutic application in the treatment of human
NSCLC. 相似文献
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Leptin increases vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), and Notch expression in cancer cells, and transphosphorylates VEGFR-2 in endothelial cells. However, the mechanisms involved in leptin’s actions in endothelial cells are not completely known. Here we investigated whether a leptin-VEGFR-Notch axis is involved in these leptin’s actions. To this end, human umbilical vein and porcine aortic endothelial cells (wild type and genetically modified to overexpress VEGFR-1 or -2) were cultured in the absence of VEGF and treated with leptin and inhibitors of Notch (gamma-secretase inhibitors: DAPT and S2188, and silencing RNA), VEGFR (kinase inhibitor: SU5416, and silencing RNA) and leptin receptor, OB-R (pegylated leptin peptide receptor antagonist 2: PEG-LPrA2). Interestingly, in the absence of VEGF, leptin induced the expression of several components of Notch signaling pathway in endothelial cells. Inhibition of VEGFR and Notch signaling significantly decreased leptin-induced S-phase progression, proliferation, and tube formation in endothelial cells. Moreover, leptin/OB-R induced transphosphorylation of VEGFR-1 and VEGFR-2 was essential for leptin’s effects. These results unveil for the first time a novel mechanism by which leptin could induce angiogenic features via upregulation/trans-activation of VEGFR and downstream expression/activation of Notch in endothelial cells. Thus, high levels of leptin found in overweight and obese patients might lead to increased angiogenesis by activating VEGFR-Notch signaling crosstalk in endothelial cells. These observations might be highly relevant for obese patients with cancer, where leptin/VEGFR/Notch crosstalk could play an important role in cancer growth, and could be a new target for the control of tumor angiogenesis. 相似文献
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Apatinib is a novel tyrosine kinase inhibitor that targets VEGFR2 signal and exhibits potent anti-tumor effects in human cancers. In this study, we aim to investigate the efficacy of Apatinib in cervical cancer. The protein expression of VEGFR2 and its relationships with clinical parameters were investigated in a panel of cervical cancer patients. In vitro, a series of experiments were performed to detect the effects of Apatinib on the proliferation, apoptosis and cell cycle in cervical cancer cells. Both the immortalized cell lines and primary cultured tissues were used to investigate the synergy between Apatinib and chemotherapeutic drugs. The in vivo effects of Apatinib were validated in a nude mouse model. Compared to that in normal cervix, VEGFR2 protein was significantly upregulated in cervical cancer tissues (P < 0.001); this was positively correlated with advanced tumor stage, lymph node metastasis, and a poor prognosis. In vitro, Apatinib markedly induced apoptosis and G1-phase arrest, suppressed cell growth, and decreased colony formation ability. We also found that primary cancer tissues with higher level of VEGFR2 were much more sensitive to Apatinib. Further, we proved that Apatinib significantly increased the sensitivity to Paclitaxel in cervical cancer cells and the mouse model. Collectively, we firstly report the anti-tumor efficacy of Apatinib in cervical cancer. Moreover, Apatinib synergized with Paclitaxel to achieve more significant suppression on tumor growth, proposing that Apatinib might be a potent drug for cervical cancer. 相似文献