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E7080 (Lenvatinib), a Multi-Targeted Tyrosine Kinase Inhibitor, Demonstrates Antitumor Activities Against Colorectal Cancer Xenografts

Please always quote using this URN: urn:nbn:de:bvb:20-opus-111165
  • Clinical prognosis of metastasized colorectal carcinoma (CRC) is still not at desired levels and novel drugs are needed. Here, we focused on the multi-tyrosine kinase inhibitor E7080 (Lenvatinib) and assessed its therapeutic efficacy against human CRC cell lines in vitro and human CRC xenografts in vivo. The effect of E7080 on cell viability was examined on 10 humanCRCcell lines and humanendothelial cells (HUVEC). The inhibitory effect of E7080 on VEGF-induced angiogenesis was studied in an ex vivo mouse aortic ring angiogenesis assay. InClinical prognosis of metastasized colorectal carcinoma (CRC) is still not at desired levels and novel drugs are needed. Here, we focused on the multi-tyrosine kinase inhibitor E7080 (Lenvatinib) and assessed its therapeutic efficacy against human CRC cell lines in vitro and human CRC xenografts in vivo. The effect of E7080 on cell viability was examined on 10 humanCRCcell lines and humanendothelial cells (HUVEC). The inhibitory effect of E7080 on VEGF-induced angiogenesis was studied in an ex vivo mouse aortic ring angiogenesis assay. In addition, the efficacy of E7080 against xenografts derived fromCRC cell lines and CRC patient resection specimenswithmutated KRASwas investigated in vivo. Arelatively low cytotoxic effect of E7080 on CRC cell viabilitywas observed in vitro. Endothelial cells (HUVEC)weremore susceptible to the incubation with E7080. This is in line with the observation that E7080 demonstrated an anti-angiogenic effect in a three-dimensional ex vivo mouse aortic ring angiogenesis assay. E7080 effectively disrupted CRC cell-mediated VEGF-stimulated growth of HUVEC in vitro. Daily in vivo treatment with E7080 (5 mg/kg) significantly delayed the growth of KRAS mutated CRC xenografts with decreased density of tumor-associated vessel formations and without tumor regression. This observation is in line with results that E7080 did not significantly reduce the number of Ki67-positive cells in CRC xenografts. The results suggest antiangiogenic activity of E7080 at a dosage thatwas well tolerated by nudemice. E7080 may provide therapeutic benefits in the treatment of CRC with mutated KRAS.show moreshow less

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Metadaten
Author: Armin Wiegering, Doreen Korb, Andreas Thalheimer, Ulrike Kämmerer, Jan Allmanritter, Niels Matthes, Michael Linnebacher, Nicolas Schlegel, Ingo Klein, Süleyman Ergün, Christoph-Thomas Germer, Christoph Otto
URN:urn:nbn:de:bvb:20-opus-111165
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I)
Medizinische Fakultät / Frauenklinik und Poliklinik
Medizinische Fakultät / Institut für Anatomie und Zellbiologie
Medizinische Fakultät / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Year of Completion:2014
Source:Neoplasia. 2014 Nov 20;16(11):972-81. doi: 10.1016/j.neo.2014.09.008
DOI:https://doi.org/10.1016/j.neo.2014.09.008
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 617 Chirurgie und verwandte medizinische Fachrichtungen
Tag:Chirurgie
Release Date:2015/03/30
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2014
Licence (German):License LogoCC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitung