Marlid Cruz-Ramos1,2, Yessica Zamudio-Cuevas3, Daniel Medina-Luna3,4, Karina Martínez-Flores3, Gabriela Martínez-Nava3, Javier Fernández-Torres3, Alberto López-Reyes5, Flavio Solca6. 1. Oncology Translational Laboratory, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain. marlid.cruz@gmail.com. 2. Cátedras de CONACYT, Instituto Nacional de Cancerología, Avenida San Fernando 22, Belisario Domínguez Secc 16, Tlalpan, 14080, Mexico City, CDMX, México. marlid.cruz@gmail.com. 3. Laboratorio de Líquido Sinovial, Instituto Nacional de Rehabilitación, Mexico City, CDMX, México. 4. Microbiology and Immunology Department, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada. 5. Laboratorio de Gerociencias, Instituto Nacional de Rehabilitación, Mexico City, CDMX, México. 6. Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.
Abstract
PURPOSE: Osteosarcoma is the most common bone tumor, mainly affecting adolescents and young adults, and metastatic disease has poor outcomes with a dismal overall survival. Currently, chemotherapy is the standard of care with limited results, finding that new therapies could improve these outcomes. Preclinical and clinical studies have suggested a possible important role of ErbB pathway aberrations in osteosarcoma etiology. The present study shows the effect of afatinib, an irreversible ErbB family blocker in osteosarcoma cell lines. METHODS: Within a panel of human osteosarcoma cell lines, we addressed cell viability assay using afatinib at increasing concentrations. Motility was measured in wound-healing assays and invasion capacity was assessed in Transwell chamber assays. Finally, to monitor ErbB pathway modulation by afatinib and related compounds, we used Western blot analyses. RESULTS: Cell viability inhibition, as well as a reduction of motility and migration of osteosarcoma cell line were observed after treatment with afatinib. Likewise, in the HOS cell line, afatinib decreased phosphorylation of key components in the ErbB signaling pathway. CONCLUSIONS: Afatinib shows relevant antitumor effect in several osteosarcoma cell lines, as it causes a significant impact on cell viability, motility, and migration with a significant decrease in the activation of ErbB pathway activity.
PURPOSE:Osteosarcoma is the most common bone tumor, mainly affecting adolescents and young adults, and metastatic disease has poor outcomes with a dismal overall survival. Currently, chemotherapy is the standard of care with limited results, finding that new therapies could improve these outcomes. Preclinical and clinical studies have suggested a possible important role of ErbB pathway aberrations in osteosarcoma etiology. The present study shows the effect of afatinib, an irreversible ErbB family blocker in osteosarcoma cell lines. METHODS: Within a panel of humanosteosarcoma cell lines, we addressed cell viability assay using afatinib at increasing concentrations. Motility was measured in wound-healing assays and invasion capacity was assessed in Transwell chamber assays. Finally, to monitor ErbB pathway modulation by afatinib and related compounds, we used Western blot analyses. RESULTS: Cell viability inhibition, as well as a reduction of motility and migration of osteosarcoma cell line were observed after treatment with afatinib. Likewise, in the HOS cell line, afatinib decreased phosphorylation of key components in the ErbB signaling pathway. CONCLUSIONS:Afatinib shows relevant antitumor effect in several osteosarcoma cell lines, as it causes a significant impact on cell viability, motility, and migration with a significant decrease in the activation of ErbB pathway activity.
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