caa a22 4500 467944954 CHVBK 20180405193736.0 cr unu---uuuuu 170328e20040101xx s 000 0 eng 10.1007/BF02665355 doi (NATIONALLICENCE)springer-10.1007/BF02665355 (NATIONALLICENCE)springer-10.1007/s00280-003-0693-x Evaluation of the antiangiogenic effect of Taxol in a human epithelial ovarian carcinoma cell line [Elektronische Daten] [Kohkichi Hata, Mitsuhiko Osaki, Dipok Dhar, Kentaro Nakayama, Ritsuto Fujiwaki, Hisao Ito, Naofumi Nagasue, Kohji Miyazaki] Purpose: Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are major ligands for the endothelium-specific tyrosine kinase receptor Tie-2 and are important regulators of endothelial cell survival. In the presence of vascular endothelial growth factor (VEGF), vessel destabilization by Ang-2 has been hypothesized to induce an angiogenic response, but in the absence of VEGF, Ang-2 leads to vessel regression. In the present study, a human ovarian cancer cell line was used to investigate the possibility that Taxol might affect the expression of Ang-1, Ang-2, and VEGF.Materials and methods: KF 28, a single-cell clone of a human ovarian epithelial carcinoma cell line, was used. The expression of Ang-1, Ang-2, and VEGF was assessed by quantitative real-time RT-PCR and Western blot analysis or enzyme-linked immunosorbent assay. Conditioned medium was used in the in vitro angiogenesis assay.Results: The concentration of Taxol that inhibited the growth of cells to the level of 50% of control cell growth was 4.65±0.35 nM. Quantitative real-time RT-PCR indicated thatAng-1 gene expression was significantly decreased by exposure to 2 nM Taxol for 168 h (P<0.05 vs control cells). Western blot analysis confirmed that the Ang-1 protein level was decreased by exposure to 2 nM Taxol for 168 h.Ang-2 gene expression did not significantly differ between control cells and those exposed to Taxol for any of the indicated times. TheAng-1/Ang-2 gene expression ratio was significantly decreased by exposure to Taxol for 168 h (P<0.05 vs control cells).VEGF gene expression was significantly decreased by exposure to Taxol for 168 h (P<0.05). The VEGF concentration in the conditioned medium was also significantly reduced by exposure to Taxol for 168 h (P<0.05). Conditioned medium collected following Taxol treatment for 168 h significantly inhibited endothelial tubule formation (P<0.05). Cell growth did not significantly differ between control cells and those exposed to Taxol for any of the indicated times.Conclusions: Our results show that exposure of ovarian cancer cells to a low concentration of Taxol may inhibit the initiating event in angiogenesis, namely, vascular regression. This information might be valuable in the development of new therapeutic interventions for epithelial ovarian cancer. Springer-Verlag, 2003 Angiopoietin-1 nationallicence Angiopoietin-2 nationallicence Vascular endothelial growth factor nationallicence Antiangiogenesis nationallicence Taxol nationallicence Hata Kohkichi Department of Obstetrics and Gynecology, Shimane Medical University, 693-8501, Izumo, Japan aut Osaki Mitsuhiko Division of organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, Yanago, Japan aut Dhar Dipok Second Department of Surgery, Shimane Medical University, Izumo, Japan aut Nakayama Kentaro Department of Obstetrics and Gynecology, Shimane Medical University, 693-8501, Izumo, Japan aut Fujiwaki Ritsuto Department of Obstetrics and Gynecology, Shimane Medical University, 693-8501, Izumo, Japan aut Ito Hisao Division of organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, Yanago, Japan aut Nagasue Naofumi Second Department of Surgery, Shimane Medical University, Izumo, Japan aut Miyazaki Kohji Department of Obstetrics and Gynecology, Shimane Medical University, 693-8501, Izumo, Japan aut Cancer Chemotherapy and Pharmacology Springer-Verlag 53/1(2004-01-01), 68-74 0344-5704 53:1<68 2004 53 280 https://doi.org/10.1007/BF02665355 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02665355 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Osaki Mitsuhiko Division of organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, Yanago, Japan aut NATIONALLICENCE 700 1- Ito Hisao Division of organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, Yanago, Japan aut NATIONALLICENCE 700 1- Hata Kohkichi Department of Obstetrics and Gynecology, Shimane Medical University, 693-8501, Izumo, Japan aut NATIONALLICENCE 700 1- Dhar Dipok Second Department of Surgery, Shimane Medical University, Izumo, Japan aut NATIONALLICENCE 700 1- Nakayama Kentaro Department of Obstetrics and Gynecology, Shimane Medical University, 693-8501, Izumo, Japan aut NATIONALLICENCE 700 1- Fujiwaki Ritsuto Department of Obstetrics and Gynecology, Shimane Medical University, 693-8501, Izumo, Japan aut NATIONALLICENCE 700 1- Nagasue Naofumi Second Department of Surgery, Shimane Medical University, Izumo, Japan aut NATIONALLICENCE 700 1- Miyazaki Kohji Department of Obstetrics and Gynecology, Shimane Medical University, 693-8501, Izumo, Japan aut NATIONALLICENCE 773 0- Cancer Chemotherapy and Pharmacology Springer-Verlag 53/1(2004-01-01), 68-74 0344-5704 53:1<68 2004 53 280 NATIONALLICENCE 700 1- Osaki Mitsuhiko Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, Yanago, Japan aut NATIONALLICENCE 856 40 https://doi.org/10.1007/s00280-003-0693-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ito Hisao Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, Yanago, Japan aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE NATIONALLICENCE NL-springer