title: Effect and mechanism of peroxisome proliferator-activated receptor-γ on the drug resistance of the U-87 MG/CDDP human malignant glioma cell line.
abstract: Peroxisome proliferator-activated receptor-γ (PPAR-γ) is important in tumor differentiation, proliferation and apoptosis. However, the effect and mechanism of PPAR-γ 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-γ. With upregulated expression of PPAR-γ, 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-β1 were decreased, expression levels of multidrug resistance related gene (MDR), multidrug resistance-associated protein and glutothionine S-transferase-π 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-γ 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.
authors.affiliation: Department of Radiation Oncology, Jinan Military General Hospital, Jinan, Shandong 250031, P.R. China.
authors.forename: Shaorong
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Radiation Oncology, Jinan Military General Hospital, Jinan, Shandong 250031, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Lv
authors.affiliation: Department of Radiation Oncology, Jinan Military General Hospital, Jinan, Shandong 250031, P.R. China.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Jinan Military General Hospital, Jinan, Shandong 250031, P.R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Gong
authors.affiliation: Department of Radiation Oncology, Jinan Military General Hospital, Jinan, Shandong 250031, P.R. China.
authors.forename: Cong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Jinan Military General Hospital, Jinan, Shandong 250031, P.R. China.
authors.forename: Anna
authors.initials: A
authors.lastname: Tong
authors.affiliation: Department of Radiation Oncology, Jinan Military General Hospital, Jinan, Shandong 250031, P.R. China.
authors.forename: Baoyi
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Jinan Military General Hospital, Jinan, Shandong 250031, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D005978:Glutathione / Q000378:metabolism; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D020112:Rhodamine 123 / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; C000595707:BCL2 protein, human; C107489:BIRC5 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051034:Inhibitor of Apoptosis Proteins; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D000077022:Survivin; D053773:Transforming Growth Factor beta1; D016159:Tumor Suppressor Protein p53; D020112:Rhodamine 123; D013940:Thymidylate Synthase; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D020169:Caspases; D005978:Glutathione; D002945:Cisplatin