Effect and mechanism of peroxisome proliferator-activated receptor-γ on the drug resistance of the U-87 MG/CDDP human malignant glioma cell line
Peroxisome proliferator-activated receptor-γ (PPAR-γ) is important in tumor differentiation, proliferation and apoptosis. However, the effect and mechanism of PPARγ on the promotion of cisplatin sensitivity in glioma cells remain to be elucidated. The present study established cisplatinresistant U87 MG/CDDP cell lines and U87 MG/CDDP cell lines overexpressing PPARγ. With upregulated expression of PPARγ, the sensitivity of cancer cells to cisplatin was increased. Flow cytometry revealed that the intracellular content of rhodamine123 was increased, expression of Pglycoprotein was downregulated, cell cycle was arrested in G0/G1 phase, apoptosis and oxidative stress was increased, levels of intracellular thymidylate synthase, glutathione and transforming growth factorβ1 were decreased, expression levels of multidrug resistance related gene (MDR), multidrug resistanceassociated protein and glutothionine Stransferaseπ were downregulated, expression levels of cell proliferation and apoptosis associated genes, including survivin and Bcell lymphoma2, were downregulated, p53, p21 and caspase3/8 were significantly upregulated, phosphorylation of extracellular signalregulated kinase and small mothers against decapentaplegic 2 were downregulated, and the transcriptional activities of Twist and nuclear factor (erythroidderived 2)like 2 were significantly reduced. The results suggested that upregulation of PPARγ in the U87 MG/DDP cells increased cisplatin sensitivity, and the underlying mechanisms included the regulation of MDR and apoptosis associated genes, which increased the intracellular accumulation of the drug, inhibited cell proliferation and promoted cell apoptosis.
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Document Type: Research Article
Affiliations: Department of Radiation Oncology, Jinan Military General Hospital, Jinan, Shandong 250031, P.R. China
Publication date: August 1, 2015
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