Function of neuronal nitric oxide synthase enzyme in temozolomide-induced damage of astrocytic tumor cells

摘要: Astrocytic tumors, including astrocytomas and glioblastomas, are the most common type of primary brain tumors. Treatment for glioblastomas includes radiotherapy, chemotherapy with temozolomide (TMZ) surgical ablation. Despite certain therapeutic advances, survival time patients is no longer than 12-14 months. Cancer cells overexpress neuronal isoform nitric oxide synthase (nNOS). In present study, it was examined whether nNOS enzyme serves a role in damage astrocytoma (U251MG U138MG) glioblastoma (U87MG) caused by TMZ. First, TMZ (250 µM) triggered an increase oxidative stress at 2, 48 72 h U87MG, U251MG U138MG cell lines, as revealed 2',7'-dichlorofluorescin-diacetate assay. The drug also reduced viability, measured MTT U87MG presented more linear decline viability time-points h, compared lines. peak occurred h. To examine NOS enzymes TMZ, N(ω)-nitro-L-arginine methyl ester (L-NAME) 7-nitroindazole (7-NI) were used. L-NAME increased while reducing preferential inhibitor 7-NI improved effects. It 12.8% decrease TMZ-injured cells. Indeed, effective restraining Silencing synthetic small interfering (si)RNA (siRNAnNOShum_4400) 20% effects 250 µM on (P<0.05). Hoechst 33342 nuclear staining confirmed that knock-down enhanced injury. conclusion, our data reveal serve produced RNA interference merits further studies animal models to disclose its potential use tumor anticancer therapy.