Dataset Information

Investigation of dacomitinib on reducing cell necrosis and enhancing cell apoptosis in C6 glioma rat model by MRI.

ABSTRACT: BACKGROUND:Glioma is one of the most epidemic and obstinate types of cancer in the central nervous system (CNS) with poor survival rate. Dacomitinib inhibited cell viability and proliferation of epidermal growth factor receptor (EGFR)-amplified glioma. In the present study, the regional effects of Dacomitinib on tumor necrosis was investigated. METHODS:A C6 rat glioma model was evaluated using proton magnetic resonance spectroscopy (1H-MRS), diffusion weighted imaging (DWI), and morphological T2-weighted imaging (T2W). The effects of Dacomitinib on glioma cells were investigated using methods of immunohistochemistry and Hematoxylin and Eosin (H&E) staining. RESULTS:The obtained data indicated that metabolite ratios were significantly decreased (all P<0.05) in the Dacomitinib-treated group compared with C6 glioma control group. The ADC value of necrotic core in Dacomitinib group was significantly lower than that in control group. In addition, the expression of Ki-67 in Dacomitinib-treated group (50.32 ± 5.61) was significantly lower than that in control group (P<0.05). The apoptotic index (AI) (28.01 ± 2.37) in Dacomitinib-treated group was significantly higher than that in control group (11.58 ± 3.17). CONCLUSION:The results demonstrated that the Dacomitinib could suppress glioma cell necrosis and proliferation.

SUBMITTER: Chen WS

PROVIDER: S-EPMC6400661 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Investigation of dacomitinib on reducing cell necrosis and enhancing cell apoptosis in C6 glioma rat model by MRI.

Chen Wang-Sheng WS Hong Lan L Wang Fei F Li Jian-Jun JJ

Bioscience reports 20190306 3

<h4>Background</h4>Glioma is one of the most epidemic and obstinate types of cancer in the central nervous system (CNS) with poor survival rate. Dacomitinib inhibited cell viability and proliferation of epidermal growth factor receptor (<i>EGFR</i>)-amplified glioma. In the present study, the regional effects of Dacomitinib on tumor necrosis was investigated.<h4>Methods</h4>A C6 rat glioma model was evaluated using proton magnetic resonance spectroscopy (<sup>1</sup>H-MRS), diffusion weighted im ...[more]

PMID: 30782784

Similar Datasets

Project description:Glioblastoma is a brain tumour frequently used as an experimental model to exploit innovative therapeutic approaches due to its high lethality and refractoriness to therapies. Part of these innovative anticancer therapies address cytoskeletal microtubules (MTs) since specific tubulin post-translational modifications (PTMs) are considered markers of tumour plasticity. In vitro studies, which traditionally employ two-dimensional (2D) culture systems, are now being replaced by three-dimensional (3D) systems that more closely mimic in vivo physiological conditions and allow a better understanding of the signalling between cells. In this work, we compared 2 liquid base 3D methods for the generation of spheroids from C6 rat glioma cells (RGCs) using 30 µL of liquid marble (LM) or the hanging drops (HDs), which contained 2 different cell numbers (5000 or 15,000). After 24 or 48 h of in vitro culture (IVC), the morphology of the spheroids was observed and the behaviour of the two main tubulin PTMs, tyrosinated α-tubulin (Tyr-T) and acetylated α-tubulin (Ac-T), was evaluated by fluorescence and Western blot (WB). RGCs spontaneously formed spherical agglomerates more rapidly in the LM than in the HD system. Cell density influenced the size of the spheroids, which reached a larger size (> of 300 µm Ø), with 15,000 cells compared to 5000 cells (150 µm Ø). Moreover, an increase in Tyr-T and Ac-T was observed in both the HD and LM system from 24 to 48 h, with the highest values shown in the 48 h/LM spheroids of 5000 cells (p < 0.05). In conclusion, by comparing the morphology and microtubular architecture of spheroids from C6 rat glioma cells developed by LM or HD methodology, our findings demonstrate that the use of a fumed silica microbioreactor boosts the induction and maintenance of a high plasticity state in glioma cells. RGCs cultured in LM express levels of tubulin PTMs that can be used to evaluate the efficacy of new anticancer therapies.

Project description:In order to establish whether growth of glioma cells is associated with glucose transport and metabolism, we investigated expression of the glucose transporter and hexokinase, as well as glucose transport and glucose phosphorylation in rat C6 glioma cells growing at different rates. Rat C6 glioma cells were subcloned to produce four different cell lines (CL1, CL2, CL3 and CL4) differing in growth, differentiation and morphology: CL1 cells were slow-growing with an astrocytic appearance whereas CL4 cells grew rapidly and were small and spindle-shaped. Immunocytochemical analysis using glial fibrillary acidic protein and galactocerebroside antibodies revealed that CL1 and CL4 cells differentiate to astrocytes and oligodendrocytes respectively. Both of these cell lines expressed GLUT1 mRNA predominantly, whereas little GLUT3 mRNA was evident by Northern-blot analysis. The GLUT1 mRNA level was much higher in CL4 than in CL1 cells, and the uptake of 2-deoxy-D-glucose and 3-O-methyl-D-glucose by CL4 cells was markedly higher than that by CL1 cells, indicating a correlation between the growth rate, glucose transporter (GLUT1) level and glucose-transport rate of C6 glioma cells. We then studied glucose metabolism by CL1 and CL4 cells by measuring their hexokinase activities and intracellular concentrations of glucose and ATP. The mitochondrial hexokinase activity of CL4 cells was about three times higher than that of CL1 cells, whereas the cytosolic hexokinase activity of CL4 cells was only about half that of CL1 cells. As the total amount of cellular hexokinase protein in CL4 cells was only slightly higher (about 20%) than that in CL1 cells, the hexokinase protein of CL4 cells was considered to have moved from the cytosol to the mitochondrial membranes. Consistent with the increased mitochondrial hexokinase activity of CL4 cells, the intracellular glucose concentration was undetectable, and the ATP concentration was higher than that of CL1 cells, suggesting that glucose transport is the rate-limiting factor for overall glucose metabolism is rapidly growing C6 cells. Therefore the present data demonstrate that glioma cell growth is related to glucose transport, which is closely associated with glucose metabolism.

Dataset Information

Investigation of dacomitinib on reducing cell necrosis and enhancing cell apoptosis in C6 glioma rat model by MRI.

Publications

Investigation of dacomitinib on reducing cell necrosis and enhancing cell apoptosis in C6 glioma rat model by MRI.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets