Targeting Fibroblast Growth Factor Receptor (FGFR) and Phosphoinositide 3-kinase (PI3K) Signaling Pathways in Medulloblastoma Cell Lines

• Published in: Anticancer research 2020-01, Vol.40 (1), p.53-66
• Main Authors: Holzhauser, Stefan, Lukoseviciute, Monika, Andonova, Teodora, Ursu, Ramona G, Dalianis, Tina, Wickström, Malin, Kostopoulou, Ourania N
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Animals; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Biotechnology; Caspase 3 - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Central nervous system; Chemotherapy; Cytotoxicity; Disease Models, Animal; Dose-Response Relationship, Drug; Fibroblast growth factor receptors; Fibroblasts; Growth factors; Humans; Inhibitors; Kinases; Medicin och hälsovetenskap; Medulloblastoma; Medulloblastoma - metabolism; Medulloblastoma - pathology; Metastases; Pediatrics; Phosphatidylinositol 3-Kinase - metabolism; Protein Kinase Inhibitors - pharmacology; Radiation; Radiation therapy; Receptors, Fibroblast Growth Factor - metabolism; Sensitivity; Signal Transduction - drug effects; Surgery; Toxicity; Tumors; Viability; Xenograft Model Antitumor Assays
• ISSN: 0250-7005; 1791-7530; 1791-7530
• DOI: 10.21873/anticanres.13925

Medulloblastoma (MB) accounts for ~20% of pediatric malignant central nervous system tumors. Treatment strategies, including surgery, radiation therapy and/or chemotherapy, are effective, but recurrence and metastasis frequently occur. Therefore, novel therapies are required. Herein, the effects of fibroblast growth factor receptor (FGFR) and phosphoinositide 3-kinase (PI3K) inhibitors on MB cells lines were evaluated. MB cell lines (UW228-3, DAOY, Med8a, D425, D283) were tested for sensitivity to FGFR (AZD4547) and PI3K (BEZ235 and BYL719) inhibitors by viability, cytotoxicity, apoptosis, and proliferation assays. Single treatments with FGFR and PI3K inhibitors decreased viability and proliferation in a dose-dependent pattern in most cell lines. Combinination of the two type of drugs, increased sensitivity, especially of the most resistant cell line UW228-3. Combination treatments with FGFR and PI3K inhibitors were superior to single treatments with FGFR and PI3K inhibitors, especially with BEZ235, for MB cell lines.