1. Down‐Regulation of AQP4 Expression via p38 MAPK Signaling in Temozolomide‐Induced Glioma Cells Growth Inhibition and Invasion Impairment
- Author
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Yaoxing Yi, Mei Yang, Hui Liu, Rong Jiang, Yuqin Chen, Xueyuan Liu, Fei Gao, Lili Kang, Yuan Li, and Jiaojiao Hou
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,MAP Kinase Signaling System ,Cell ,Down-Regulation ,Biology ,p38 Mitogen-Activated Protein Kinases ,Biochemistry ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Glioma ,Temozolomide ,medicine ,Humans ,Neoplasm Invasiveness ,MTT assay ,Molecular Biology ,Aquaporin 4 ,medicine.diagnostic_test ,Cell Biology ,Cell cycle ,medicine.disease ,Neoplasm Proteins ,Cell biology ,Dacarbazine ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Signal transduction ,medicine.drug - Abstract
Glioma is the most common and lethal central nervous system tumors. Temozolomide (TMZ) is an effective drug for malignant glioma, however, the intracellular and molecular mechanisms behind this anti-cancer effect have yet to be fully understood. The aim of the present study was to determine whether TMZ inhibits proliferation, invasion of glioma cells in vitro and whether these effects can be mediated through modulation of aquaporin 4 (AQP4) and phosphorylation of the MAPK pathway. The viability of U87 and U251 human glioma cells was evaluated using MTT assay. The cell cycle distribution was detected with flow cytometry. Migration ability and invasion ability were tested by scratch assays and transwell assays, respectively. The levels of AQP4 and MAPK were measured using immunoblot analyses. Our results showed that TMZ inhibited proliferation, migration and invasion, and induced G2/M arrest in U87 and U251 glioma cell lines. These changes were associated with a decrease in the levels of AQP4 expression as well as activation phosphorylated level of p38. Treatment with a p38 chemical activator (anisomycin) resulted in similar effects as TMZ treatment on glioma cells. And p38 chemical inhibitor (SB203580) could block these effects in glioma treated with TMZ, suggesting a direct up-regulation of the p38 signaling pathway. Therefore, we identified that TMZ might have therapeutic potential for controlling proliferation, invasion of malignant glioma by inhibiting AQP4 expression through activation of p38 signal transduction pathway. J. Cell. Biochem. 118: 4905-4913, 2017. © 2017 Wiley Periodicals, Inc.
- Published
- 2017