Long Non-coding RNA EPIC1 Promotes Cell Proliferation and Motility and Drug Resistance in Glioma.

Evidence has revealed that long non-coding RNAs (lncRNAs) are involved in carcinogenesis and tumor progression. lncRNAs play an important role in regulation of numerous cellular processes including cell proliferation, apoptosis, cell cycle, differentiation, and motility. Several studies have demonstrated that lncRNA EPIC1 governs cell growth, cell cycle, migration, invasion, and drug resistance in human malignancies. However, the role of EPIC1 and its underlying molecular mechanisms in glioma have not been investigated. In this study, we determined the function of EPIC1 in glioma cells via upregulation or downregulation of EPIC1. We further dissected the mechanism of EPIC1-mediated tumor progression in glioma. Our results showed that inhibition of EPIC1 suppressed cell viability, induced apoptosis, inhibited cell invasion, and increased cell sensitivity to temozolomide in glioma cells. Consistently, overexpression of EPIC1 exhibited the opposite effects in glioma cells. Moreover, our data suggest that EPIC1 exerts its biological functions via targeting Cdc20 in glioma cells. In line with this, overexpression of Cdc20 reversed the EPIC1-mediated tumor progression in glioma cells. Therefore, targeting EPIC1 might be a useful approach for glioma treatment.

Cdc20 overexpression is involved in temozolomide-resistant glioma cells with epithelial-mesenchymal transition.

Glioma remains one of the most aggressive and lethal cancers in central nervous system. Temozolomide (TMZ) is the most commonly used chemotherapeutic agent in gliomas. However, therapeutic benefits of TMZ could be very limited and all patients would finally suffer from tumor progression as the tumors develop resistance to TMZ. In this study, we aim to investigate the underlying mechanism of chemoresistance in glioma cell line and to identify whether there is still a close link between epithelial-mesenchymal transition (EMT) and TMZ resistance in gliomas. The real-time RT-PCR and Western blotting were used to measure the expression of EMT markers in TMZ-resistant cells. The migration and invasion assays were conducted to detect the cell motility activity in TMZ-resistant cells. The transfection was used to down-regulate the Cdc20 expression. The student t-test was applied for data analysis. We established stable TMZ-resistant glioma cells and designated as TR. Our results revealed that TR cells exhibited a significantly increased resistance to TMZ compared with their parental cells. Moreover, TMZ-resistant cells had acquired EMT-like changes. For the mechanism study, we measured a significant increased expression of CDC20 and decreased expression of Bim in TR cells. Moreover, upon suppression of CDC20 by shRNA transfection, TR cells underwent a reverse of EMT features. Importantly, knockdown of CDC20 enhanced the drug sensitivity of TR cells to TMZ. Our results suggested that inactivation of CDC20 could contribute to the future therapy that possibly overcomes drug resistance in human cancers.

Mild hypothermia protects against early brain injury in rats following subarachnoid hemorrhage via the TrkB/ERK/CREB signaling pathway.

Subarachnoid hemorrhage (SAH) is a severe neurological disease, which is associated with a significant number of cases of premature mortality and disability worldwide. Mild hypothermia (MH) has been proposed as a potential therapeutic strategy to reduce neuronal injury following SAH. The present study aimed to investigate the mechanisms of MH's protective role in the process of SAH. The present study demonstrated that MH was able to protect against early brain injury in a rat model of SAH. Treating SAH rats with MH reduced the release of reactive oxygen species and prevented activation of apoptotic cascades. Furthermore, the protective effects of MH were shown to be mediated by enhanced activity of the tropomyosin receptor kinase B/extracellular signal­regulated kinases/cAMP response element binding protein (TrkB/ERK/CREB) pathway. Inhibition of TrkB/ERK/CREB activity using a small molecule inhibitor largely abolished the beneficial effects of MH in SAH rats. These results outline an endogenous mechanism underlying the neuroprotective effects of MH in SAH.

Linalool Inhibits LPS-Induced Inflammation in BV2 Microglia Cells by Activating Nrf2.

Linalool, a natural compound of the essential oils, has been reported to have anti-inflammatory effects. This study aimed to investigate the anti-inflammatory effects and mechanism of linalool in LPS-stimulated BV2 microglia cells. BV2 microglia cells were stimulated with LPS in the presence or absence of linalool. The production of inflammatory mediators TNF-α, IL-1ß, NO, and PGE2 as well as Nrf2, HO-1 expression were detected. Our results showed that linalool inhibited LPS-induced TNF-α, IL-1ß, NO, and PGE2 production in a dose-dependent manner. Linalool also inhibited LPS-induced NF-κB activation. Treatment of linalool induced nuclear translocation of Nrf2 and expression of HO-1. In addition, our results showed that the anti-inflammatory effect of linalool was attenuated by transfection with Nrf2 siRNA. In conclusion, these results suggested that linalool inhibits LPS-induced inflammation in BV2 microglia cells by activating Nrf2/HO-1 signaling pathway.

Association between glutathione S-transferase T1 null genotype and glioma susceptibility: a meta-analysis.

The relationship between genetic polymorphisms of glutathione S-transferase (GST) and the development of glioma has been investigated in several epidemiologic studies. However, these studies report inconsistent results. In order to get this precise result, a meta-analysis was conducted by calculating the pooled odds ratios (OR) and the 95% confidence intervals (95 % CI). Eleven case-control research studies with a total of 2,416 glioma cases and 4,850 controls were included into this meta-analysis. The combined results based on all studies showed that there was no significant association between the GSTT1 null allele and glioma risk (OR = 1.188, 95% CI = 0.929­1.520, P(heterogeneity) = 0.003, P = 0.170). In the subgroup analysis, the same results were found in our work. There was no risk of publication bias in this meta-analysis. Our results suggest that GSTT1 null genotype was not associated with the increased risk of glioma.

Effects of tetrandrine on glioma cell malignant phenotype via inhibition of ADAM17.

Tetrandrine (TET), a bisbenzylisoquinoline alkaloid isolated from the root of Hang-Fang-Chi (Stephania tetrandra S. Moore), exhibits broad pharmacological effects, including antitumor activity in various malignant neoplasms. Recently, the beneficial effects of TET on cytotoxicity towards tumor cells, radiosensitization, circumventing multidrug resistance, normal tissue radioprotection, and antiangiogenesis have been examined extensively. However, the potential molecular mechanisms of the effect on glioma of TET are yet unknown. This study is explored to evaluate whether TET can inhibit cell proliferation, invasion, and the possible underlying mechanisms in glioma U87 cell. In the present study, cell proliferation was determined by using the Cell Counting Kit-8 (CCK-8) viability assay. The invasion and migration were evaluated by means of wound-scratch assay and Matrigel-Transwell methods. The mRNA expression and protein expression of ADAM metallopeptidase domain 17 (ADAM17) in glioma cell lines and glioma samples were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. Moreover, the expression of epidermal growth factor receptor (EGFR)/p-EGFR and AKT/p-AKT was studied to clarify the molecular mechanism. Our results suggested that TET inhibited cell proliferation in a dose- and time-dependent manner, and cell migration and invasion in vitro. In addition, our results indicated that ADAM17 expression significantly increased in glioma compared to nontumored human brain tissue and according to the histopathological grade of glioma. Western blot analysis showed that protein expressions of ADAM17, p-EGFR, and p-AKT were inhibited by TET in U87 cells. These data also suggest that suppression of ADAM17 and downregulation of EGFR-phosphoinositide-3-kinase (PI3K)-AKT signaling pathways may contribute to TET-induced decrease of proliferation, migration, and invasiveness.

Inhibitory effect of Pulsatilla chinensis polysaccharides on glioma.

Malignant glioma is a very devastating disease. Conventional surgery, radio-and chemotherapy are of limited benefit to improve the cure of patients with malignant astrocytomas. In this research, we evaluated the inhibitory effect of Pulsatilla chinensis polysaccharides (PCPS) on glioma in vivo and in vitro. PCPS had a significant anti-proliferative effect on C6 glioma in vitro assay. Meanwhile a remarkable inhibitory effect PCPS on the growth of C6 glioma and prolongation of life survival could be observed in vivo, comparable to carmustine (BCNU) administration. Moreover PCPS treatment to tumor bearing mice could not only decrease the body weight loss, but also elevate the thymus and spleen indices. In addition, PCPS administration to tumor bearing mice could relieve the liver and kidney damage with decreased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and urea, and enhance superoxide dismutase (SOD) and catalase (CAT) enzyme activities with lower MDA levels in the plasma of tumor bearing mice. The above data proved that PCPS had strong antitumor activity and could be considered as a possible candidate drugs for the glioma therapy.