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-gamma ( PPAR-gamma) is important in tumor differentiation, proliferation and apoptosis. However, the effect and mechanism of PPAR-gamma on the promotion of cisplatin sensitivity in glioma cells remain to be elucidated. The present study established cisplatin-resistant U-87 MG/CDDP cell lines and U-87 MG/CDDP cell lines overexpressing PPAR-gamma. With upregulated expression of PPAR-gamma, the sensitivity of cancer cells to cisplatin was increased. Flow cytometry revealed that the intracellular content of rhodamine-123 was increased, expression of P-glycoprotein 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 factor-beta 1 were decreased, expression levels of multidrug resistance related gene (MDR), multidrug resistance-associated protein and glutothionine S-transferase-p were downregulated, expression levels of cell proliferation and apoptosis associated genes, including survivin and B-cell lymphoma-2, were downregulated, p53, p21 and caspase-3/8 were significantly upregulated, phosphorylation of extracellular signal-regulated kinase and small mothers against decapentaplegic 2 were downregulated, and the transcriptional activities of Twist and nuclear factor (erythroid-derived 2)-like 2 were significantly reduced. The results suggested that upregulation of PPAR-gamma in the U-87 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.