title: Opposite angiogenic outcome of curcumin against ischemia and Lewis lung cancer models: in silico, in vitro and in vivo studies.
abstract: The aim of this study was to investigate the angiogenic effects of curcumin on an ischemia and lung cancer model. To induce ischemia combined with lung cancer models, unilateral femoral arteries of C57BL/6 mice were disconnected on one side of the mouse and Lewis lung carcinoma (LLC) cells were xenografted on the opposite side. Angiogenic effects and underlying mechanisms associated with curcumin were investigated. Molecular target(s), signaling cascades and binding affinities were detected by Western blot, two-dimensional gel electrophoresis (2-DE), computer simulations and surface plasmon resonance (SPR) techniques. Curcumin promoted post-ischemic blood recirculation and suppressed lung cancer progression in inbred C57BL/6 mice via regulation of the HIF1α/mTOR/VEGF/VEGFR cascade oppositely. Inflammatory stimulation induced by neutrophil elastase (NE) promoted angiogenesis in lung cancer tissues, but these changes were reversed by curcumin through directly reducing NE secretion and stimulating α1-antitrypsin (α1-AT) and insulin receptor substrate-1 (IRS-1) production. Meanwhile, curcumin dose-dependently influenced endothelial cells (EC) tube formation and chicken embryo chorioallantoic membrane (CAM) neovascularization. Curcumin had opposite effects on blood vessel regeneration under physiological and pathological angiogenesis, which was effected through negative or positive regulation of the HIF1α/mTOR/VEGF/VEGFR cascade. Curcumin had the promise as a new treatment modality for both ischemic conditions and lung cancer simultaneously in the clinic.
authors: State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China. Electronic address: herryvan@sohu.com.
authors: Shengjun
authors: S
authors: Fan
authors: State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China. Electronic address: yan_xu81@yahoo.com.cn.
authors: Yan
authors: Y
authors: Xu
authors: State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China. Electronic address: lixin0837@163.com.
authors: Xin
authors: X
authors: Li
authors: State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China. Electronic address: tielu@bjmu.edu.cn.
authors: Lu
authors: L
authors: Tie
authors: State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China. Electronic address: pannay26@bjmu.edu.cn.
authors: Yan
authors: Y
authors: Pan
authors: State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China. Electronic address: xjli@bjmu.edu.cn.
authors: Xuejun
authors: X
authors: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D049033:Chorioallantoic Membrane; D003198:Computer Simulation; D003474:Curcumin / Q000494:pharmacology*; D015180:Electrophoresis, Gel, Two-Dimensional; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D020349:Surface Plasmon Resonance; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D058570:TOR Serine-Threonine Kinases; D003474:Curcumin
keywords: Angiogenesis; Curcumin; Ischemia and lung cancer model; Neutrophil elastase