Norcantharidin: a potential antiangiogenic agent for gallbladder cancers in vitro and in vivo

Autor: Jing-Tao Zhang, Zhe-Ming Zhao, Yue-Zu Fan, Chun-Qiu Chen, Wei Sun
Rok vydání: 2011
Předmět:
Male
Vascular Endothelial Growth Factor A
Cancer Research
Pathology
Time Factors
Angiogenesis
Angiogenesis Inhibitors
Apoptosis
Chick Embryo
Polymerase Chain Reaction
Chorioallantoic Membrane
Neovascularization
chemistry.chemical_compound
Mice
Cell Movement
Tube formation
Mice
Inbred BALB C
Norcantharidin
Neovascularization
Pathologic
Matrigel Invasion Assay
Flow Cytometry
Immunohistochemistry
Tumor Burden
Oncology
cardiovascular system
Female
Gallbladder Neoplasms
medicine.symptom
medicine.medical_specialty
Perfusion Imaging
Mice
Nude
Neovascularization
Physiologic
Biology
Angiopoietin-2
In vivo
Cell Line
Tumor
medicine
Human Umbilical Vein Endothelial Cells
Animals
Humans
Cell Proliferation
Tissue Inhibitor of Metalloproteinase-2
Oncogene
Dose-Response Relationship
Drug
Bridged Bicyclo Compounds
Heterocyclic
Xenograft Model Antitumor Assays
Rats
chemistry
Regional Blood Flow
Cancer research
Thrombospondins
Magnetic Resonance Angiography
Zdroj: International journal of oncology. 40(5)
ISSN: 1791-2423
Popis: Our objective was to explore the antiangiogenic activity of norcantharidin (NCTD) as an angiogenic inhibitor for gallbladder cancers. In vitro and in vivo experiments to determine the effects of NCTD on HUVECs, chicken CAM capillaries and gallbladder cancer xenograft angiogenesis in nude mice were respectively done. The MTT method was used to assay the cytotoxicity of NCTD on HUVECs. Immunofluorescence was used to evaluate HUVEC apoptosis. The scraping line method, matrigel invasion assay and tube formation assay were used to detect the migration, invasion and tube formation of HUVECs. A digital camera was used to observe chicken CAM capillaries. Experiments with NCTD in a xenograft model were used to observe the effect of NCTD on xenograft growth and survival of mice with xenografts. CD₃₄ immunohistochemistry, flow cytometry and micro-MRA were used, respectively, to determine MVD, cell apoptosis and hemodynamic analysis of the xenografts. Immunohistochemistry and RT-PCR were used, respectively, to detect the expression of VEGF, Ang-2, TSP, TIMP-2 proteins/mRNAs of the xenografts. The xenograft MVD associated with tumor volume, the PCNA/apoptosis ratio and related-protein expression was evaluated simultaneously. We found that NCTD effectively inhibited the proliferation, migration, invasion and capillary-like tube formation of HUVECs in vitro; it reduced angiogenesis and directly destroyed the formed CAM capillaries in vivo. In the experiments in mice, NCTD not only inhibited significantly xenograft proliferation and growth, prolonged survival time of mice with xenografts, decreased the xenograft MVD and vascular perfusion, but also, similarly to ES, decreased significantly the expression of VEGF or Ang-2 protein/mRNA, increased the expression of TSP or TIMP-2 protein/mRNA. Moreover, the xenograft MVD was positively related with tumor volume, PCNA/apoptosis ratio, and VEGF or Ang-2 expression, respectively (all P
Databáze: OpenAIRE
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