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 prove