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Published on: June 26, 2019
Afatinib is active in osteosarcoma in osteosarcoma cell lines
Marlid Cruz-Ramos1,2, Yessica Zamudio-Cuevas3, Daniel Medina-Luna3,4
1Oncology Translational Laboratory, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain. marlid.cruz@gmail.com.
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.
Insights
Afatinib, an ErbB family blocker, demonstrated significant antitumor effects in osteosarcoma cell lines by reducing cell viability, motility, and migration. This study highlights afatinib
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Osteosarcoma is a prevalent bone tumor in adolescents and young adults.
- Metastatic osteosarcoma has poor prognosis, necessitating novel therapeutic strategies.
- Aberrations in the ErbB pathway are implicated in osteosarcoma development.
Purpose of the Study:
- To investigate the anti-cancer effects of afatinib, an ErbB family blocker, on osteosarcoma cell lines.
- To evaluate afatinib's impact on osteosarcoma cell viability, motility, and migration.
- To assess afatinib's modulation of the ErbB signaling pathway in osteosarcoma.
Main Methods:
- Cell viability assays were performed on human osteosarcoma cell lines treated with varying concentrations of afatinib.
- Wound-healing and Transwell chamber assays were used to measure cell motility and invasion.
- Western blot analysis was employed to monitor ErbB pathway modulation by afatinib.
Main Results:
- Afatinib treatment led to significant inhibition of cell viability in osteosarcoma cell lines.
- A reduction in the motility and migration capacity of osteosarcoma cells was observed.
- Afatinib decreased the phosphorylation of key signaling components within the ErbB pathway in the HOS cell line.
Conclusions:
- Afatinib exhibits a notable antitumor effect against multiple osteosarcoma cell lines.
- The drug significantly impacts osteosarcoma cell viability, motility, and migration.
- Afatinib effectively reduces ErbB pathway activity, suggesting its therapeutic potential in osteosarcoma.
