Afatinib is active in osteosarcoma in osteosarcoma cell lines
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ORIGINAL ARTICLE – CANCER RESEARCH
Afatinib is active in osteosarcoma in osteosarcoma cell lines Marlid Cruz‑Ramos1,4 · Yessica Zamudio‑Cuevas2 · Daniel Medina‑Luna2,5 · Karina Martínez‑Flores2 · Gabriela Martínez‑Nava2 · Javier Fernández‑Torres2 · Alberto López‑Reyes6 · Flavio Solca3 Received: 9 February 2020 / Accepted: 15 April 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords Osteosarcoma · Afatinib · ErbB · Antitumoral
Introduction Marlid Cruz-Ramos and Yessica Zamudio-Cuevas authors have equally contributed to this work as first authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00432-020-03220-y) contains supplementary material, which is available to authorized users. * Marlid Cruz‑Ramos [email protected] 1
Oncology Translational Laboratory, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
2
Laboratorio de Líquido Sinovial, Instituto Nacional de Rehabilitación, Mexico City, CDMX, México
3
Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria
4
Cátedras de CONACYT, Instituto Nacional de Cancerología, Avenida San Fernando 22, Belisario Domínguez Secc 16, Tlalpan, 14080 Mexico City, CDMX, México
5
Microbiology and Immunology Department, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada
6
Laboratorio de Gerociencias, Instituto Nacional de Rehabilitación, Mexico City, CDMX, México
Osteosarcoma (OS) is the most common bone tumor, affecting mainly teenagers and young adults (Mirabello et al. 2009; Ottaviani and Jaffe 2009). Multidrug chemotherapy and tumor surgery are the standards of ca
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