[Retracted] Deoxypodophyllotoxin inhibits cell viability and invasion by blocking the PI3K/Akt signaling pathway in human glioblastoma cells.

Following the publication of the above article and a corrigendum that was published to address issues of duplicated data panels in Fig. 4 (doi: 10.3892/or.2023.8484), a concerned reader has drawn to the Editor's attention that Fig. 3B also contains a matching pair of identical flow cytometry scatterplots where the results from different experiments were intended to have been portrayed, and certain of the western blotting data shown in Fig. 3C are strikingly similar to data that had appeared in Figs. 2 and 3 in a previously published paper written by different authors at different research institutes [Tian F, Ding D and Li D: Fangchinoline targets PI3K and suppresses PI3K/AKT signaling pathway in SGC7901 cells. Int J Oncol 46: 2355­2363, 2015]. In view of the fact that certain of the data in the above article had already appeared in a previously published paper, and given the large number of apparently overlapping data panels identified in several of the figures, the Editor of Oncology Reports has decided that this paper should be retracted from the publication. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 41: 2453­2463, 2019; DOI: 10.3892/or.2019.7016].

[Retracted] miR­489 promotes apoptosis and inhibits invasiveness of glioma cells by targeting PAK5/RAF1 signaling pathways.

Subsequently to the publication of the article, an interested reader drew to the authors' attention that certain of the data panels showing the results of cell migration and invasion assays in Figs. 5A and 6C were overlapping, suggesting that the data were derived from the same original source, even though they were selected to represent the results from differently performed experiments. The authors requested that a corrigendum be published to rectify this problem; however, after having conducted an independent analysis of the data in the Editorial Office, we have noticed that the data shown in Figs. 5A and 6C are strikingly similar to data appearing in different form in other articles published in another journal, mainly written by different authors at different research institutions. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere at the time it was submitted to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 42: 2390­2401, 2019; DOI: 10.3892/or.2019.7381].

[Corrigendum] Deoxypodophyllotoxin inhibits cell viability and invasion by blocking the PI3K/Akt signaling pathway in human glioblastoma cells.

Following the publication of the above article, a concerned reader drew to the authors' attention that various pairs of the data panels shown for the Transwell migration assays in Fig. 4A­D on p. 2459 featured overlapping data, such that a number of the panels may have been derived from the same original sources. The authors have examined their original data, and realize that errors were inadvertently made during the assembly of these figure parts. The authors have reassembled Fig. 4 containing alternative data in Fig. 4A­D, and the revised version of this figure is shown on the next page. Note that the revised data shown for this figure do not affect the overall conclusions reported in the paper. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of 1 for allowing them the opportunity to publish this. They also apologize to the readership for any inconvenience caused. [Oncology Reports 41: 2453­2463, 2019; DOI: 10.3892/or.2019.7016].

Scinderin Is a Novel Oncogene for Its Correlates with Poor Prognosis, Immune Infiltrates and Matrix Metalloproteinase-2/9 (MMP2/9) in Glioma.

PURPOSE: The effect of scinderin (SCIN) on cancer progression has been studied, but its role in glioma remains unknown. This study describes the value of SCIN for the diagnosis, prognosis, and treatment of glioma. METHODS: The expression of SCIN was analyzed using the GEPIA, Oncomine, cBioPortal, and CGGA databases. GO/KEGG enrichment analysis of similar genes to SCIN were performed using the R software package, and the protein-protein interaction (PPI) network was analyzed by the STRING and GeneMANIA databases. The correlations of mRNA expression between SCIN and MMP2/9 were analyzed by TCGA glioma. Simultaneously, the TISIDB and TIMER databases were used to analyze the correlation between SCIN and immune infiltration. Finally, SCIN and MMP2/9 protein expression among different grades of glioma was performed and the results were obtained via immunohistochemistry and Western blot assays. We used the Kaplan-Meier method and Cox proportional hazards model to assess the impact of SCIN and MMP2/9 on glioma patients' survival. The correlations between SCIN and MMP2/9 were analyzed by immunohistochemistry and Western blot assays. RESULTS: SCIN was upregulated in glioma patients with a poor prognosis. The GO and KEGG enrichment analysis showed the functional relationship between SCIN and the immune cell activation and regulation. In addition, the expression of SCIN was related to MMP2/9 in glioma. The correlation analysis showed that SCIN expression was associated with tumor purity and immune infiltration. SCIN and MMP2/9 are negative prognostic factors resulting in worsening glioma patients' survival. CONCLUSION: Our studies demonstrated that SCIN expression was associated with MMP2/9, immune infiltration, and a poor prognosis in glioma. SCIN may serve as a potential prognostic marker and an immune therapy target for glioma.

Malignant solitary fibrous tumor in the central nervous system treated with surgery, radiotherapy and anlotinib: A case report.

BACKGROUND: Solitary fibrous tumor (SFT) of the central nervous system is rare. It is predominantly benign and rarely malignant. There is no established standardized treatment regimen for malignant intracranial SFTs. CASE SUMMARY: We present a rare case of SFT in a 9-year-old girl with a space-occupying effect in the frontal-parietal lobes. She underwent craniotomy, and the mass was resected. Immunohistochemistry examination of the specimen showed that Ki-67 proliferation index staining was highly positive in 80% of tumor cells. Whole exome sequencing of the surgical tissue showed 38 somatic gene mutations and 1 gene amplification such as fibroblast growth factor receptor 4 or TP53. At 1.5 mo after surgery, head magnetic resonance imaging revealed that the tumor had recurred. The patient received 60 Gy and 30 fractions of intensity modulated radiotherapy. The patient then received anlotinib 8 mg po qd for 1-14 d of a 21 d cycle. Following this regimen, the patient achieved stable disease for > 17 mo. Magnetic resonance imaging at 1.5 year after surgery showed that the tumor had not progressed. CONCLUSION: This is the first reported case of SFT of the central nervous system treated with surgery, radiotherapy and anlotinib. This regimen may be an effective treatment option for malignant intracranial SFT patients.

The impact of COVID-19 on business perspectives of sustainable development and corporate social responsibility in China.

The new coronavirus (COVID-19) has generated an unprecedented degree of social and economic impact on the planet, but few researchers have explored the repercussion of COVID-19 for sustainable development (SD) and corporate social responsibility (CSR), especially from the perspective of Chinese businesses. This paper is the first to outline the priority changes of both SD and CSR over the period of COVID-19 incidence in China. An online questionnaire survey of 1161 owners and managers of Chinese companies was conducted, and respondents were asked to score the priorities of their company over the pre, during and post COVID-19 periods. The research was carried out at the end of the first COVID-19 wave in China but during the period of lockdown in some parts of the country. It was found that there was a priority change regarding three dimensions of sustainable development and 13 aspects of CSR. While the social dimension of SD was prioritized during and post COVID-19, the environmental dimension was the only one deemed to be less important and less prioritized over the longer term after the pandemic. The top three short-term CSR priorities were having in place a workplace health and safety plan, engaging in philanthropic activities and protecting biodiversity, and the top three longer-term CSR priorities were job creation, protecting biodiversity and having in place a workplace health and safety plan. Environmental protection and using clean energy were not reported as a CSR priority. The paper concludes that China's recovery mode cannot be called 'green' and suggests ways this could be changed.

Co-overexpression of RIOK1 and AKT1 as a prognostic risk factor in glioma.

Glioblastoma multiforme (GBM) is one of the most frequent primary malignancies of the brain. Although the treatment strategy has significantly improved, patient prognosis remains poor. In vitro studies have shown that the right open reading frame kinase 1/protein kinase B (RIOK1-AKT) signaling pathway plays an important role in the malignant phenotype of glioma cells. This study aimed to investigate the co-expression of RIOK1 and ATK in glioma tissues and its clinical significance. Compared with normal tissues, RIOK1 and AKT1 expression were significantly upregulated in glioma tissues. In addition, patients with higher World Health Organization staging grades had increased RIOK1 and AKT1 expression levels, and RIOK1 and AKT1 expression were positively correlated. Notably, both RIOK1 and AKT1 expressions were correlated with poor prognosis. In vitro experiments showed that silencing RIOK1 inhibited the proliferation, migration, and invasion of glioma cell lines by suppressing AKT and c-Myc expression. These results indicate that the RIOK1-AKT1 axis could play an important role in GBM progression.

Two Different Minimally Invasive Surgery Puncture Points with Thrombolysis in a Patient with Bilateral Basal Ganglia Hemorrhages.

Bilateral basal ganglia hemorrhages are extremely rare and have very poor prognosis. We describe the case of a 52-year-old woman with a history of hypertension who experienced bilateral basal ganglia hemorrhages. We performed bilateral hematoma aspiration by minimally invasive surgery via frontal and temporal puncture points. We discuss the surgical procedure and review relevant literature pertaining to the underlying causes and complications of similar cases.

Waste Separation Behaviour of College Students under a Mandatory Policy in China: A Case Study of Zhengzhou City.

The need for effective solid waste management (SWM) is an important environmental and public health issue. As a key way of minimizing municipal solid waste (MSW), source separation has in recent years become the centre of discussion in China. Following the example of Shanghai, the city of Zhengzhou introduced its mandatory waste separation measures on 1 December 2019. But does the mandatory regulation work? This study aims to investigate the waste separation behaviour of college students in Zhengzhou under the mandatory regulation and the motivations behind students' behaviour. A questionnaire-based survey was carried out on 62 university campuses in Zhengzhou City, and a total of 1747 valid questionnaires were completed across these campuses and analysed. It was found that under Zhengzhou's mandatory measures, college students do have a basic knowledge of waste separation and most are familiar with where kitchen waste should be placed, but they have problems categorizing some recyclables such as glass, hazardous waste such as lightbulbs and other waste such as cigarette butts and napkins. It was also found that college students' waste separation behaviour, their attitude towards waste separation and the convenience of waste sorting facilities in Zhengzhou in the mandatory era have been improved compared to the era prior to mandatory waste separation. The results also indicate that most of college students (86.7%) always or sometimes undertake waste separation, and students majoring in science and senior year undergraduates are more likely to participate in the practice of waste separation. Other influencing factors of college students' waste separation behaviour include convenience of waste sorting facilities, their willingness to separate waste, knowledge of a related field, attitude towards waste separation, peer pressure as well as the existence of a reward and penalty system. Management strategies for improving college students' waste separation behaviour under mandatory regulation are also discusses and a number of recommendations for improvement are made.

miR­489 promotes apoptosis and inhibits invasiveness of glioma cells by targeting PAK5/RAF1 signaling pathways.

Glioma patients receiving therapy are at a high risk of relapse and rapid progression and, thus, more effective treatments are required. The aim of the present study was to determine the suppressive role of miR­489 as an alternative therapeutic target for preventing glioma progression. The results of the present study demonstrated that patients with relatively lower levels of expression of miR­489 had more favorable clinical outcomes. Furthermore, miR­489 expression was inversely correlated with p21­activated kinase 5 (PAK5) mRNA expression levels in glioma specimens. A dual luciferase reporter assay revealed that miR­489 suppressed PAK5 expression by directly targeting the PAK5 3'­untranslated region. The effects of miR­489 on cell viability were measured using MTT and Cell Counting Kit­8 assays. The results demonstrated that ectopic expression of miR­489 mimic decreased cell viability by interfering with cyclin D1 and c­Myc signaling. Additionally, the effect of miR­489 on apoptosis was determined using Hoechst 33258 staining and flow cytometry. The results demonstrated that miR­489 decreased the activity of RAF1, reduced Bcl­2 and promoted Bax expression, resulting in increased cell apoptosis. Furthermore, the effect of miR­489 mimic on cellular motility was assessed using migration and invasion assays. miR­489 was shown to abolish the PAK5/RAF1/MMP2 pathway, resulting in decreased cell invasion ability. These results indicated that miR­489 may be involved in PAK5­mediated regulation of glioma progression, demonstrating the potential therapeutic benefits of targeting miR­489 in glioma.

Deoxypodophyllotoxin inhibits cell viability and invasion by blocking the PI3K/Akt signaling pathway in human glioblastoma cells.

Deoxypodophyllotoxin (DPT) is a natural chemical that has been demonstrated to inhibit cellular viability and motility in various cancer cell types. Although previous studies have indicated that programmed cell death and cell cycle arrest are involved in the suppression of glioma development by DPT, the underlying mechanism has not been fully explored. Different methods were used to the elucidate the mechanisms of DPT that inhibit the malignant behavior of glioma cells. Cellular viability was assessed by MTT assay. Relative protein and mRNA expression levels were detected by western blot analysis and reverse transcription­quantitative polymerase chain reaction analyses, respectively. Cell cycle distribution and the apoptosis rate were detected by flow cytometry. Hochest 33258 staining was also performed to detect apoptosis. Transwell assays without and with Matrigel were used to assess migration and invasion abilities, respectively. It was determined that DPT suppressed cellular viability by inducing cell cycle arrest at the G1/S phase by targeting the phosphatidylinositol 4,5­bisphosphate 3­kinase (PI3K)/RAC­α serine/threonine­protein kinase (Akt)­cyclin­dependent kinase inhibitor 1­cyclin­dependent kinase 2/cyclin E signaling cascades. Additionally, DPT significantly enhanced apoptosis by attenuating the PI3K/Akt­mediated suppression of Bcl­2­associated agonist of cell death expression, which was accompanied by an increased apoptosis regulator BAX/apoptosis regulator Bcl­2 ratio. Furthermore, DPT downregulated the invasiveness of glioma cells by hindering PI3K/Akt­matrix metalloproteinase (MMP)9/MMP2 signaling pathways. In conclusion, DPT effectively inhibited the expression of PI3K and downregulated PI3K/Akt­mediated signaling pathways to prevent glioblastoma progression.

MAGI1 Inhibits the Proliferation, Migration and Invasion of Glioma Cells.

BACKGROUND: Membrane-associated guanylate kinase inverted repeat member 1 (MAGI1) acts as a tumor suppressor in a variety of tumors; however, its expression and biological function in glioma are still unknown. METHODS: MAGI1 expression in glioma was examined by immunohistochemistry. In addition, overexpression of MAGI1 in U87 and U373 cells, colony formation and MTT assays were used to evaluate cell proliferation, Transwell assays to determine cell migration and invasion, and a xenograft model established using U87 cells to evaluate the effect of MAGI1 overexpression in vivo. Western blot assays were used to analyze the Akt, MMP2, MMP9 and E-cadherin/N-cadherin/vimentin pathway changes after overexpression of MAGI1. RESULTS: We demonstrated that MAGI1 was expressed at low levels in glioma. Low MAGI1 expression was positively correlated with the malignant progression of glioma and indicated a poor prognosis. Moreover, we found that overexpressed MAGI1 inhibited the proliferation, migration and invasion of glioma cells by regulating cell growth and EMT through Akt, MMP2, MMP9 and the E-cadherin/N-cadherin/vimentin pathway. CONCLUSION: These findings demonstrate a novel function of MAGI1 in glioma progression and suggest that MAGI1 might be a target for the diagnosis and treatment of glioma.

KDM2B overexpression correlates with poor prognosis and regulates glioma cell growth.

BACKGROUND: Gliomas are one of the most lethal cancers in the human central nervous system. Despite clinical treatment advancements, the prognosis of patients with glioma remains poor. KDM2B is a histone lysine demethylase, which has been observed in multiple tumors. But the concrete role of KDM2B in gliomas remains to be further illustrated. METHODS: The KDM2B expression in gliomas was detected with immunohistochemistry and Western blot assay. Furthermore, knockdown of KDM2B in U87 and U251 glioma cell lines, the proliferation capacity was evaluated by cell viability assay, colon formation assay and flow cytometry in vitro. Western blot assay was used to analyze the p21, EZH2 and cyclinD1 changes followed by knockdown of KDM2B. RESULTS: KDM2B was upregulated in tissues of glioma patients, and the expression was correlated to cancer progression. Downregulation of KDM2B in U87 and U251 glioma cell lines inhibited cell proliferation and arrested cell cycle in G0/G1 phase. In addition, silencing KDM2B promoted the upregulation of p21 while reduced the expression of EZH2 and cyclinD1. CONCLUSION: Taken together, our results revealed that KDM2B might influence gliomas growth and act as a novel therapeutic target for glioma patients.

TGF-β2 enhances invasion ability of glioma stem cell through matrix metalloproteinase pathway / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To study the effect and possible mechanism of TGF-β2 on the invasion of glioma stem cells (GSCs). Methods: Tumor tissues of 8 patients with glioblastoma multiforme, who underwent resection at Department of Neurosurgery of the FirstAffiliated Hospital of China Medical University duringApril 2016 toApril 2017, were collected. The primary culture of glioma cells were conducted with trypsin digestion. Partial primary glioma cells were seeded into serum-free DMEM/F12 culture medium containing EGF, bFGF and B27 to obtain suspension of tumor spheres. Immunoflurenscent staining and differentiation assay were used to detect whether the tumor spheres were GSCs. TGF-β2 secretion ability of GSCs was determined by ELISAassay.After transfection of TGF-β2 siRNA, the invasion ability of glioma stem cells was determined by Transwell assay. Western blotting was used to examine the effect of TGF-β2 on expression of matrix metalloproteinases (MMP) in glioma stem cells. Results: The suspended tumor spheres were proved to be GSCs by immunofluorescent staining and differentiation assay; the tumor spheres expressed the marker of GSCs（CD133）and had the ability to multi-differentiate (glia and neuronal cells). Compared with the primary glioma cells, Glioma stem cells exerted significantly improved TGF-β2 secretion ability ([74.13±3.63] vs [46.13±2.61] pg/ml, P<0.05); and TGF-β2 silencing significantly reduced the invasion ability of glioma stem cells ([105.71±8.69] vs [63.67±5.93], P<0.05) and inhibited MMP-2 and MMP-9 expressions. Conclusion: TGF-β2 can promote the invasiveness of glioma stem cells through MMP-2 and MMP-9 pathway.

Expression of zinc transporter 1 gene in brain glioma tissues and its effects on proliferation, migration and invasion of glioma U87 cell line / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To detect the expression of zinc transporter 1 (ZnT1) gene in glioma tissue, and to explore its effect on the proliferation, migration and invasion of U87 cells. Methods: From October 2015 to January 2017, 20 patients with glioma, who received no chemoradiotherapy before operation, were collected from Department of Neurosurgery, the First Affiliated Hospital of China Medical University. The protein and mRNA content of ZnT1 in glioma tissues and adjacent tissues were detected by Western blotting and Realtime PCR, respectively. ZnT1 and si-ZnT1 plasmids were transfected into glioma U87 cell line respectively to construct ZnT1 over-expression U87 cell line and ZnT1 knockdown U87 cell line. The effects of ZnT1 on proliferation, migration and invasion of U87 cells were detected by MTT and transwell assay. Results: Both mRNA and protein expressions of ZnT1 in glioma tissues was significantly higher than those in adjacent tissues (all P<0.05). U87 cell lines with ZnT1 over-expression and knockdown were successfully constructed. Compared with the control group and empty plasmid control group, the proliferation (0.54±0.01 vs 0.45±0.04, 0.43±0.03, P<0.01), invasion and migration (all P<0.05) of U87 cells with ZnT1 over-expression were significantly increased at 12 h after transfection; however, the proliferation (0.37±0.03 vs 0.45±0.01, 0.44±0.03, P<0.01), invasion and migration (all P<0.05) of U87 cells with ZnT1 knockdown were decreased significantly. Conclusion: ZnT1 was highly expressed in glioma tissues, and promoted the proliferation, migration and invasion of glioma U87 cells.

Temozolomide increases MHC-I expression via NF-κB signaling in glioma stem cells.

Gliomas are the most common and primary tumors of the central nervous system in adults. Temozolomide (TMZ) is the main drug used to treat glioma; however, prognosis remains poor for most patients. Glioma stem cells (GSCs) are thought to enable glioma initiation and evasion from immune surveillance; their immunogenicity can be determined by expression of major histocompatibility complex (MHC)-I. The present study investigated the effect of TMZ on MHC-I expression in GSCs. Glioma spheres were cultured in serum-free medium containing epidermal growth factor, basic fibroblast growth factor, and B27; MHC-I expression was detected by immunocytochemistry, quantitative real-time PCR, and flow cytometry. Nuclear factor (NF)-κB expression in glioma stem cells was detected by Western blot. TMZ enhanced MHC-I expression in GSCs, and NF-κB was activated. TMZ treatment increased MHC-I expression via modulation of NF-κB signaling in GSCs. In addition to being a chemotherapeutic agent, TMZ may also serve as an immunomodulatory agent in the treatment of glioma patients.

Nanoscale TiO2 nanotubes govern the biological behavior of human glioma and osteosarcoma cells.

Cells respond to their surroundings through an interactive adhesion process that has direct effects on cell proliferation and migration. This research was designed to investigate the effects of TiO2 nanotubes with different topographies and structures on the biological behavior of cultured cells. The results demonstrated that the nanotube diameter, rather than the crystalline structure of the coatings, was a major factor for the biological behavior of the cultured cells. The optimal diameter of the nanotubes was 20 nm for cell adhesion, migration, and proliferation in both glioma and osteosarcoma cells. The expression levels of vitronectin and phosphor-focal adhesion kinase were affected by the nanotube diameter; therefore, it is proposed that the responses of vitronectin and phosphor-focal adhesion kinase to the nanotube could modulate cell fate. In addition, the geometry and size of the nanotube coating could regulate the degree of expression of acetylated α-tubulin, thus indirectly modulating cell migration behavior. Moreover, the expression levels of apoptosis-associated proteins were influenced by the topography. In conclusion, a nanotube diameter of 20 nm was the critical threshold that upregulated the expression level of Bcl-2 and obviously decreased the expression levels of Bax and caspase-3. This information will be useful for future biomedical and clinical applications.

Correlations of ANP genetic polymorphisms and serum levels with ischemic stroke risk: a meta-analysis.

AIMS: This meta-analysis was performed to evaluate the correlations between atrial natriuretic peptide (ANP) genetic polymorphism and its serum ANP levels with the risk of ischemic stroke. METHODS: The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before October 1st, 2013 without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios (ORs) or standardized mean difference (SMD) with their 95% confidence interval (95% CI) were calculated. Twelve case-control studies that met all inclusion criteria were included in this meta-analysis. A total of 1285 patients with ischemic stroke and 1088 healthy control subjects were involved in this meta-analysis. Three common single-nucleotide polymorphisms (1837 G/A, 2238 T/C, and 664 G/A) in the ANP gene were assessed. RESULTS: Our meta-analysis results revealed that ANP 2238 T/C polymorphism might increase the risk of ischemic stroke (C allele vs. T allele: OR=2.26, 95% CI: 1.59-3.23, p<0.001; TC+CC vs. TT: OR=2.26, 95% CI: 1.34-3.81, p=0.002; respectively). However, we found no correlations of ANP 1837 G/A and 664 G/A polymorphisms with ischemic stroke risk (all p>0.05). Furthermore, ischemic stroke patients had higher levels of serum ANP than those of healthy control subjects (SMD=3.12, 95% CI: 1.16-5.07, p=0.002). Our study revealed no publication bias in this meta-analysis (all p>0.05). CONCLUSION: Our findings indicate that ANP genetic polymorphism and serum ANP levels may contribute to the development of ischemic stroke. Thus, the ANP genetic polymorphism and serum ANP levels could be potential biomarkers for early detection of ischemic stroke.

Interleukin-6 is overexpressed and augments invasiveness of human glioma stem cells in vitro.

In the present study, we carried out a series of assays to investigate the expression of interleukin-6 in glioma stem cells and its role in glioma stem cells invasion. Glioma stem cells from eight surgical glioma specimens were cultured and identified. Real-time reverse transcription polymerase chain reaction and immunoassay were used to measure and compare the expression levels of interleukin-6 in glioma stem cells and matched primary glioma cells. Subsequently, neutralizing antibody against interleukin-6 or exogenous interleukin-6 was used in a Matrigel-invasion assay and effects of interleukin-6 on glioma stem cells invasiveness was then determined. The results revealed that interleukin-6 mRNA and protein expression levels were significantly higher in glioma stem cells than in primary glioma cells from the same tumor. However, its expression levels were not apparently higher in glioma stem cells from grade IV gliomas than from grade III gliomas. In Matrigel-invasion assay, glioma stem cells invasiveness markedly decreased after interleukin-6 was blocked with neutralizing antibody, but significantly increased when exogenous interleukin-6 was added. Additionally, the similar effects of interleukin-6 were also found on primary glioma cells invasiveness. Our results suggest that glioma stem cells are likely to be the major tumor source of immunosuppressive cytokines interleukin-6 and thereby play a crucial role in determining glioma malignancy, immunosuppression and immune evasion. Furthermore, interleukin-6 can significantly augment glioma stem cells invasiveness in vitro, suggesting a potential target in future therapy for glioma stem cells rather than for their derivatives.

TRAIL and paclitaxel synergize to kill U87 cells and U87-derived stem-like cells in vitro.

U87-derived stem-like cells (U87-SLCs) were cultured using serum-free stem cell media and identified by both biological behaviors and markers. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and paclitaxel (PX), in combination or alone, was used to treat U87-MG human glioma cells (U87 cells) or U87-SLCs. The results showed that TRAIL/PX cannot only synergistically inhibit U87 cells but also U87-SLCs. We observed a significantly higher apoptotic rate in U87 cells simultaneously treated with TRAIL/PX for 24 h compared to cells treated with either drug alone. Furthermore, there was a remarkably higher apoptosis rate in U87-SLCs induced by the TRAIL/PX combination compared with either drug alone. Unlike the simultaneous treatment in U87 cells, U87-SLCs were pretreated for 24 h with 1 µmol/L of PX followed by 1000 ng/mL of TRAIL. Protein assays revealed that TRAIL/PX synergy was related to DR4, cleaved caspase-8 and cleaved caspase-3 upregulation, whereas the mitochondrial pathway was not involved in TRAIL-induced apoptosis. The present study indicates that PX can sensitize U87 cells and U87-SLCs to TRAIL treatment through an extrinsic pathway of cell apoptosis. The combined treatment of TRAIL and PX may be a promising glioma chemotherapy because of its successful inhibition of U87-SLCs, which are hypothesized to influence chemotherapeutic outcomes of gliomas.