Astrocytoma ; genetics ; metabolism ; Brain Neoplasms ; genetics ; metabolism ; Frizzled Receptors ; genetics ; metabolism ; Glioblastoma ; genetics ; metabolism ; Glioma ; genetics ; metabolism ; Humans ; Paraffin Embedding ; RNA, Messenger ; metabolism ; Receptors, G-Protein-Coupled ; genetics ; metabolism ; Signal Transduction ; Wnt2 Protein ; genetics ; metabolism ; beta Catenin ; genetics ; metabolism

To investigate the inhibitory effect and anti-cancer mechanism of adenovirus mediated IL-24 gene expression on the human U251 glioma cell. U251 glioma cells were infected with Ad-IL-24 at various multiplicity of infection (MOIs). Cell proliferation was determined by MTT assay. Cell apoptosis was detected by flow cytometry and Hochest staining. The transcription of apoptosis-related genes was analyzed by reverse transcription-PCR (RT-PCR), and the expression of Cleaved Caspase-3 was analyzed by Western blotting. The result showed that the growth of U251 glioma cells was significantly inhibited by Ad-IL-24 at the MOI of 100. The apoptotic rate of U251 glioma cells was 42% 72 h after infection with Ad-IL-24. Four days after infection, the growth of the U251 glioma cells was inhibited to 50%. RT-PCR showed that Ad-IL-24 not only up-regulated expression of bax/bcl-2, ICE, C-myc, p53 and down-regulated the expression of HIF-1alpha, but also enhanced Caspase-3 activation, eventually resulting apoptosis. Taken together, these results suggest that infection of U251 glioma cells with Ad-IL-24 can inhibit growth and induce apoptosis significantly by the regulation of apoptosis-related genes.
Adenoviridae ; genetics ; metabolism ; Apoptosis ; Brain Neoplasms ; genetics ; pathology ; Cell Proliferation ; drug effects ; Genetic Therapy ; Glioma ; genetics ; pathology ; Humans ; Interleukins ; genetics ; metabolism ; Recombination, Genetic ; Tumor Cells, Cultured

DNA Methylation ; Glioma ; metabolism ; Humans ; O(6)-Methylguanine-DNA Methyltransferase ; genetics ; Polymerase Chain Reaction ; methods ; Promoter Regions, Genetic ; genetics

Nerve growth factor (NGF) is mainly secreted by the neuroglia cells, which can exert biological effect through its receptors on the specific target cell surface. NGF is closely related to neurocyte growth, differentiation and apoptosis. As a neurotropic virus, HSV-1 an easily lead to neurocyte, neuroglia cells death or apoptosis. In this study, the U251 human glioma cells were chosen as target cells to study the change of NGF and its receptors in the apoptosis process of HSV-1 infection. Our results showed that U251 cells were permissive to HSV-1 replication. In the apoptosis process of HSV-1 infected U251 cells, the expression of both NGF and P75NTR increased and then decreased, while the expression of TrkA decreased gradually. These result indicated that HSV-1 was able to induce the abnormal expression of NGF and its receptors in U251 cells.
Apoptosis ; Cell Line, Tumor ; Gene Expression ; Glioma ; genetics ; metabolism ; physiopathology ; virology ; Herpes Simplex ; genetics ; metabolism ; physiopathology ; virology ; Herpesvirus 1, Human ; genetics ; physiology ; Humans ; Nerve Growth Factor ; genetics ; metabolism ; Receptor, Nerve Growth Factor ; genetics ; metabolism ; Receptor, trkA ; genetics ; metabolism ; Virus Replication

Animals ; Antigens, Neoplasm ; genetics ; metabolism ; Biomarkers, Tumor ; genetics ; metabolism ; Brain Neoplasms ; metabolism ; Cell Adhesion Molecules ; genetics ; metabolism ; Digestive System Neoplasms ; metabolism ; Female ; Genital Neoplasms, Female ; metabolism ; Glioma ; metabolism ; Head and Neck Neoplasms ; metabolism ; Humans ; Immunotherapy ; Male ; Prostatic Neoplasms ; metabolism ; Signal Transduction

At this time, brain tumor stem cells remain a controversial hypothesis while malignant brain tumors continue to present a dire prognosis of severe morbidity and mortality. Yet, brain tumor stem cells may represent an essential cellular target for glioma therapy as they are postulated to be the tumorigenic cells responsible for recurrence. Targeting oncogenic pathways that are essential to the survival and growth of brain tumor stem cells represents a promising area for developing therapeutics. However, due to the multiple oncogenic pathways involved in glioma, it is necessary to determine which pathways are the essential targets for therapy. Furthermore, research still needs to comprehend the morphogenic processes of cell populations involved in tumor formation. Here, we review research and discuss perspectives on models of glioma in order to delineate the current issues in defining brain tumor stem cells as therapeutic targets in models of glioma.
1-Phosphatidylinositol 3-Kinase/genetics/metabolism ; Animals ; Brain Neoplasms/genetics/*metabolism/*pathology/therapy ; Glioma/genetics/*metabolism/*pathology/therapy ; Humans ; Neoplastic Stem Cells/*metabolism/*pathology ; Receptors, Notch/genetics/metabolism ; Signal Transduction/genetics/physiology

OBJECTIVETo study the role of survivin gene in the invasive behavior of glioma cells and explore the possible mechanism.

METHODSThe mRNA and protein expressions of survivin in glioma cell line SNB19 transfected by small interfering RNA (siRNA) targeting survivin were determined by real time RT-PCR and Western blotting, respectively. The anchorage-independent growth of the cells was examined by clone formation assay in soft agar, and their invasiveness was evaluated using a Boyden chamber model. The protein level of urokinase-type plasminogen activator (uPA) was also determined by western blotting.

RESULTSSurvivin siRNA dose-dependently inhibited the anchorage-independent growth and invasiveness and reduced the expression of uPA protein in SNB19 cells.

CONCLUSIONRNA interference targeting survivin can inhibit the invasiveness of glioma cells in vitro possibly by down-regulating uPA expression.

Brain Neoplasms ; genetics ; pathology ; Cell Line, Tumor ; Glioma ; genetics ; pathology ; Humans ; Inhibitor of Apoptosis Proteins ; Microtubule-Associated Proteins ; genetics ; metabolism ; Neoplasm Invasiveness ; genetics ; RNA Interference ; RNA, Messenger ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; Urokinase-Type Plasminogen Activator ; genetics ; metabolism

OBJECTIVETo study the expression of RAS protein in human glioma tissues and its influence on tumor growth.

METHODSRAS protein expression in glioma tissues was determined by immunohistochemical (IHC) staining. Subsequently, MTT cell proliferation assay, flow cytometry and Western blotting were used to assay U251 cells with reduced RAS expression.

RESULTSThe expression of RAS in glioma was increased and strongly correlated with pathological grade. Downregulation of RAS resulted in glioma cells growth suppression and increased apoptosis.

CONCLUSIONThe expression level of RAS protein in human glioma was increased. Downregulation of RAS can inhibit glioblastoma cell growth through the RAS signal pathway.

Brain Neoplasms ; genetics ; metabolism ; pathology ; Cell Growth Processes ; genetics ; Cell Line, Tumor ; Down-Regulation ; Glioma ; genetics ; pathology ; Humans ; Immunohistochemistry ; ras Proteins ; biosynthesis ; genetics

OBJECTIVETo study the expression of FOS protein in human glioma tissues and its effect on tumor growth.

METHODSFOS protein expression in glioma tissues was determined with immunohistochemical (IHC) staining. Subsequently, 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide (MTT) assay, flow cytometry, transwell invasion and Western blotting were used to assay U87 and U251 cells with reduced FOS expression.

RESULTSThe expression of FOS in glioma was increased and strongly correlated with its pathological grade. Abrogating expression of FOS has suppressed proliferation and invasion, and delayed cell cycle at G1 phrase for both U87 and U251 cells.

CONCLUSIONThe expression of FOS protein in human glioma was strong. FOS protein probably plays a critical role in the progression of gliomas.

Cell Line, Tumor ; Cell Movement ; genetics ; Cell Proliferation ; Cyclin D1 ; genetics ; metabolism ; Gene Expression ; Glioma ; genetics ; metabolism ; pathology ; Humans ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Neoplasm Grading ; Proto-Oncogene Proteins c-fos ; genetics ; metabolism ; RNA Interference

OBJECTIVETo investigate the effect of osteopontin silencing on the invasion and apoptosis of U251 cells.

METHODSThe invasion, apoptosis and levels of uPA, MMP-2 and MMP-9 were determined by invasion assay, flow cytometry, Western blot and real-time fluorescence quantitative PCR respectively.

RESULTSOsteopontin small interference RNA (siRNA) inhibited osteopontin expression and cell invasion, promoted apoptosis in U251 cells. In addition, the expression of Bcl-2, uPA, MMP-2 and MMP-9 was decreased, while Bax level was elevated.

CONCLUSIONOsteopontin siRNA can inhibit U251 cells invasion via the down-regulation of uPA, MMP-2 and MMP-9 levels, and promote apoptosis through induction of Bax expression and inhibition of Bcl 2 level. It suggests that osteopontin plays an important role in human glioma progression.

Apoptosis ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Gene Transfer Techniques ; Genetic Vectors ; genetics ; metabolism ; Glioma ; genetics ; metabolism ; pathology ; physiopathology ; Humans ; Lentivirus ; genetics ; metabolism ; Neoplasm Invasiveness ; Osteopontin ; genetics ; metabolism ; RNA, Small Interfering ; genetics