Evaluation of Insulin-mediated Regulation of AKT Signaling in Childhood Acute Lymphoblastic Leukemia
| Autor: | Hongman Xue, Chun Chen, Jian Wang, Hong-Gui Xu, Shao-Fen Lin, Xi-Kang Tang, Yan-Ru Chen |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Cell Apoptosis Jurkat cells Receptor IGF Type 1 Jurkat Cells 03 medical and health sciences Antineoplastic Agents Immunological 0302 clinical medicine medicine Asparaginase Humans Insulin Child Protein kinase B PI3K/AKT/mTOR pathway business.industry Cell growth Akt/PKB signaling pathway Daunorubicin Receptors Somatomedin Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.anatomical_structure Oncology Drug Resistance Neoplasm Vincristine Child Preschool 030220 oncology & carcinogenesis Pediatrics Perinatology and Child Health Cancer research Female Signal transduction business Proto-Oncogene Proteins c-akt Signal Transduction 030215 immunology |
| Zdroj: | Journal of Pediatric Hematology/Oncology. 41:96-104 |
| ISSN: | 1077-4114 |
| Popis: | OBJECTIVE Hyperglycemia increases the risk of early recurrence and high mortality in some adult blood cancers. In response to increased glucose levels, insulin is secreted, and several studies have shown that insulin-induced AKT signaling can regulate tumor cell proliferation and apoptosis. The AKT pathway is aberrantly activated in adult acute lymphoblastic leukemia (ALL), but the mechanisms underlying this activation and its impact in pediatric patients with ALL are unclear. MATERIALS AND METHODS We evaluated the insulin-induced chemoresistance and AKT pathway activation by measuring cell proliferation, apoptosis, and other parameters in ALL cell lines (Jurkat and Reh cells), as well as in primary pediatric leukemic cell samples, after culture with insulin, the chemotherapeutic drugs daunorubicin (DNR), vincristine (VCR), and L-asparaginase (L-Asp), or anti-insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody. RESULTS DNR, VCR, and L-Asp-induced toxicity in Jurkat and Reh cells was reduced in the presence of insulin. DNR promoted cell proliferation, whereas DNR, VCR, and L-Asp all reduced apoptosis in both cell lines cotreated with insulin compared with that in cell lines treated with chemotherapeutics alone (P |
| Databáze: | OpenAIRE |
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