Oncology Translational Laboratory, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.
Cátedras de CONACYT, Instituto Nacional de Cancerología, Avenida San Fernando 22, Belisario Domínguez Secc 16, Tlalpan, 14080, Mexico City, CDMX, México.
J Cancer Res Clin Oncol. 2020 Jul;146(7):1693-1700. doi: 10.1007/s00432-020-03220-y. Epub 2020 Apr 24.
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.
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.
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.
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.
骨肉瘤是最常见的骨肿瘤，主要影响青少年和年轻人，转移性疾病的总体生存率较差。目前，化疗是标准的治疗方法，但效果有限，因此需要寻找新的治疗方法来改善这些结果。临床前和临床研究表明，表皮生长因子受体（ErbB）通路异常在骨肉瘤的发病机制中可能起着重要作用。本研究显示了 afatinib（一种不可逆的 ErbB 家族阻滞剂）在骨肉瘤细胞系中的作用。
在一组人骨肉瘤细胞系中，我们用递增浓度的 afatinib 进行细胞活力测定。用划痕愈合试验测量迁移能力，用 Transwell 室试验评估侵袭能力。最后，用 Western blot 分析来监测 afatinib 和相关化合物对 ErbB 通路的调节。
用 afatinib 处理后，观察到骨肉瘤细胞系的细胞活力抑制、迁移和迁移减少。同样，在 HOS 细胞系中，afatinib 降低了 ErbB 信号通路关键成分的磷酸化。
afatinib 在几种骨肉瘤细胞系中显示出相关的抗肿瘤作用，因为它对细胞活力、迁移和迁移有显著影响，同时显著降低了 ErbB 通路的活性。
