Objective: To investigate the mechanisms of action of the tumoricidal effects of temozolomide against the human glioma cell line U251 in vitro, and to provide preclinical proof-of-concept studies of the effects of temozolomide-containing regimens. Methods: U251 cells were exposed to 100 mmol/l temozolomide. Morphological alterations were monitored by light microscopy. Cell viability was measured using the 3 -(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle analysis and the rate of apoptosis were determined using flow cytometry and the number of acidic vesicular organelles stained with acridine orange were analysed by fluorescence microscopy. The scratch recovery test was used to measure cell migration. Results: U251 cells that were treated with temozolomide displayed morphological alterations indicative of a rounder shape and impaired cellular adhesion to the cell culture plate compared with control U251 cells. Temozolomide reduced cell viability as measured by the MTT assay, caused cell cycle arrest in the gap 2/mitosis phase, inhibited cell migration and promoted autophagy in U251 cells. Conclusion: Temozolomide induced autophagic, but not apoptotic processes, in U251 cells and thus reduced their viability and migration.

No abstract

Dysfunction of the microRNA (miR) network has been indicated as a major regulator in neurological diseases. However, there is limited understanding regarding the functional significance of miRs in ischemic brain injury. In the present study, miR-196a expression was significantly increased in rat brains and neurons following transient middle cerebral artery occlusion (MCAO) or oxygen-glucose deprivation, respectively. In addition, repression of miR-196a significantly decreased neuron cell apoptosis and the infarct size in rats subjected to MCAO (P<0.05). Furthermore, miR-196a was indicated to directly target and inhibit high mobility group A1 expression, which indicated a potential role for miR-196a in ischemic brain injury. These findings suggested that miR-196a may be involved in regulating neuronal cell death, thus offering a novel target for the development of therapeutic agents against ischemic brain injury.

No abstract