Trifluoperazine prevents FOXO1 nuclear excretion and reverses doxorubicin-resistance in the SHG44/DOX drug-resistant glioma cell line
| Autor: | Yuan Cheng, Xiaoquan Luo, Xiaozhong Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Cell cycle checkpoint Cell Survival Cell Mice Nude Apoptosis doxorubicin 03 medical and health sciences Mice 0302 clinical medicine multidrug resistance Cell Line Tumor Genetics medicine polycyclic compounds Animals Humans Doxorubicin Forkhead box O1 Oncogene trifluoperazine Chemistry Caspase 3 Forkhead Box Protein O1 General Medicine Articles Cell Cycle Checkpoints Glioma Cell cycle Flow Cytometry Immunohistochemistry 030104 developmental biology medicine.anatomical_structure Tumor progression Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research Intracellular medicine.drug |
| Zdroj: | International Journal of Molecular Medicine |
| ISSN: | 1791-244X 1107-3756 |
| Popis: | As a tumor suppressor, Forkhead box O1 (FOXO1) is located in the nucleus where it regulates gene expression and inhibits tumor progression. However, the antitumor effects of FOXO1 are attenuated in several tumors due to its translocation from the nucleus to the cytoplasm. Trifluoperazine (TFP) is able to reverse tumor drug resistance by inhibiting multidrug resistance (MDR), however, the detailed molecular mechanisms by which this occurs remain to be fully elucidated. In the present study, the doxorubicin (DOX)‑resistant SHG44/DOX glioma cell line was established. The results showed that TFP promoted DOX‑induced cytotoxicity, cell cycle arrest and early apoptosis using a Cell Counting Kit‑8 and flow cytometry. In vivo experiments also demonstrated that DOX combined with TFP reduced tumor volumes and proliferation indices, and led to higher protein levels of FOXO1. In addition, TFP inhibited the nuclear exclusion of FOXO1, contributing toward the downregulation of MDR genes and an increase in intracellular DOX concentrations by reverse transcription‑quantitative polymerase chain reaction, western blot analysis, immunofluorescence and spectrophotometer analysis. Therefore, TFP may inhibit DOX resistance by stimulating FOXO1 nuclear translocation and suppressing MDF genes in SHG44/DOX cells, contributing to promising clinical prospects for tumor chemotherapy. |
| Databáze: | OpenAIRE |
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