Effects of Sorafenib, a Tyrosin Kinase Inhibitor, on Adrenocortical Cancer
| العنوان: | Effects of Sorafenib, a Tyrosin Kinase Inhibitor, on Adrenocortical Cancer |
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| المؤلفون: | Roberta Maggio, Pina Lardo, Barbara Bucci, Antonio Stigliano, Donatella Amendola, Salvatore Raffa, Lidia Cerquetti, Elisa Petrangeli, Giuseppe Pugliese, Vincenzo Toscano, Maria Rosaria Torrisi |
| المصدر: | Frontiers in Endocrinology, Vol 12 (2021) Frontiers in Endocrinology |
| بيانات النشر: | Frontiers Media S.A., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Sorafenib, neoangiogenesis, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Antineoplastic Agents, spheroids, Tyrosine-kinase inhibitor, Diseases of the endocrine glands. Clinical endocrinology, Metastasis, epithelium-mesenchymal transition, 03 medical and health sciences, Endocrinology, 0302 clinical medicine, matrix metalloproteinase-9, Adrenocortical Carcinoma, Tumor Cells, Cultured, medicine, Humans, Adrenocortical carcinoma, Neoplasm Invasiveness, Viability assay, adrenal cancer, neoplasms, Cell Proliferation, Original Research, Kinase, business.industry, Cell Cycle, apoptosis, intercellular junctions, sorafenib, medicine.disease, RC648-665, Adrenal Cortex Neoplasms, digestive system diseases, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Apoptosis, Cell culture, 030220 oncology & carcinogenesis, Cancer research, business, medicine.drug |
| الوصف: | The lack of an effective medical treatment for adrenocortical carcinoma (ACC) has prompted the search for better treatment protocols for ACC neoplasms. Sorafenib, a tyrosine kinase inhibitor has exhibited effectiveness in the treatment of different human tumors. Therefore, the aim of this study was to understand the mechanism through which sorafenib acts on ACC, especially since treatment with sorafenib alone is sometimes unable to induce a long-lasting antiproliferative effect in this tumor type. The effects of sorafenib were tested on the ACC cell line H295R by evaluating cell viability, apoptosis and VEGF receptor signaling which was assessed by analyzing VE-cadherin and β-catenin complex formation. We also tested sorafenib on an in vitro 3D cell culture model using the same cell line. Apoptosis was observed after sorafenib treatment, and coimmunoprecipitation data suggested that the drug prevents formation VEGFR-VE-cadherin and β-catenin proteins complex. These results were confirmed both by ultrastructural analysis and by a 3D model where we observed a disaggregation of spheres into single cells, which is a crucial event that represents the first step of metastasis. Our findings suggest that although sorafenib induces apoptotic cell death a small portion of cells survive the treatment and have characteristics of a malignancy. Based on our data we recommend against the use of sorafenib in patients with ACC. |
| اللغة: | English |
| تدمد: | 1664-2392 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a9a43cf900188973048200d299c3a1cbTest https://www.frontiersin.org/articles/10.3389/fendo.2021.667798/fullTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a9a43cf900188973048200d299c3a1cb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16642392 |
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