title: Inhibition of basal JNK activity by small interfering RNAs enhances cisplatin sensitivity and decreases DNA repair in T98G glioblastoma cells.
abstract: Inhibition of basal Jun kinase (JNK) activity by small interfering RNAs (siRNAs) enhances cisplatin sensitivity and decreases DNA repair in T98G glioblastoma cells. Although the JNK pathway has been extensively studied in recent years, little is known concerning the signaling pathways that control their expression in glioma cells. The aim of the present study was to assess the role of c-Jun-NH2-terminal kinases (JNKs) in the regulation of T98G glioblastoma cells treated with cisplatin in the presence or absence of siRNAs against JNK1 and JNK2. Addition of either small interfering JNK1-siRNA or JNK2-siRNA induced decreased DNA repair and sensitized the T98G glioblastoma cells to the DNA damaging drug cisplatin (cis-diamminedichloroplatinum). This effect was associated with reduced cell survival and loss of anchorage‑independent colony formation. The results indicate that effective inhibition of the JNK pathway significantly sensitizes glioblastoma cells to cisplatin, a compound of proven clinical value whose spectrum of application is limited by resistance phenomena.
authors.affiliation: Laboratory of Experimental Biomedicine, University of Tarapaca, Campus Esmeralda, Iquique, Chile.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Parra
authors.affiliation: Faculty of Sciences, Arturo Prat University, Iquique, Chile.
authors.forename: Luis
authors.initials: L
authors.lastname: Gutiérrez
authors.affiliation: Programme of Molecular and Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, Independencia, Santiago, Chile.
authors.forename: Jorge
authors.initials: J
authors.lastname: Ferreira
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D048688:MAP Kinase Kinase 7 / Q000235:genetics / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; C000595707:BCL2 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D048031:JNK Mitogen-Activated Protein Kinases; D048055:Mitogen-Activated Protein Kinase 8; D048688:MAP Kinase Kinase 7; C482569:MAP2K7 protein, human; D002945:Cisplatin