RND1 inhibits epithelial-mesenchymal transition and temozolomide resistance of glioblastoma via AKT/GSK3-ß pathway.

GBM is one of the most malignant tumor in central nervous system. The resistance to temozolomide (TMZ) is inevitable in GBM and the characterization of TMZ resistance seriously hinders clinical treatment. It is worthwhile exploring the underlying mechanism of aggressive invasion and TMZ resistance in GBM treatment. Bioinformatic analysis was used to analyze the association between RND1 and a series of EMT-related genes. Colony formation assay and cell viability assay were used to assess the growth of U87 and U251 cells. The cell invasion status was evaluated based on transwell and wound-healing assays. Western blot was used to detect the protein expression in GBM cells. Treatment targeted RND1 combined with TMZ therapy was conducted in nude mice to evaluate the potential application of RND1 as a clinical target for GBM. The overexpression of RND1 suppressed the progression and migration of U87 and U251 cells. RND1 knockdown facilitated the growth and invasion of GBM cells. RND1 regulated the EMT of GBM cells via inhibiting the phosphorylation of AKT and GSK3-ß. The promoted effects of RND1 on TMZ sensitivity was identified both in vitro and in vivo. This research demonstrated that the overexpression of RND1 suppressed the migration and EMT status by downregulating AKT/GSK3-ß pathway in GBM. RND1 enhanced the TMZ sensitivity of GBM cells both in vitro and in vivo. Our findings may contribute to the targeted therapy for GBM and the understanding of mechanisms of TMZ resistance in GBM.

BCAS3 accelerates glioblastoma tumorigenesis by restraining the P53/GADD45α signaling pathway.

As in many other cancers, highly malignant proliferation and disordered cell division play irreplaceable roles in the exceedingly easy recurrence and complex progression of glioblastoma multiforme (GBM); however, mechanistic studies of the numerous regulators involved in this process are still insufficiently thorough. The role of BCAS3 has been studied in other cancers, but its role in GBM is unclear. Here, our goal was to investigate the expression pattern of BCAS3 in GBM and its potential mechanism of action. Using TCGA database and human GBM samples, we found that BCAS3 expression was up-regulated in GBM, and its high expression predicted poor prognosis. To further investigate the relationship between BCAS3 and GBM characteristics, we up-regulated and down-regulated BCAS3 expression in GBM to detect its effect on cell proliferation and cell cycle. At the same time, we established U87 cells stably overexpressing BCAS3 and generated an intracranial xenograft model to investigate the Potential role of BCAS3 in vivo. Finally, based on in vitro cell experiments and in vivo GBM xenograft models, we observed that BCAS3 significantly regulates GBM cell proliferation and cell cycle and that this regulation is associated with p53/GADD45α Signaling pathway. Taken together, our findings suggest that BCAS3 is inextricably linked to the progression of GBM and that targeting BCAS3 may have therapeutic effects in GBM patients.

Rho family GTPase 1 (RND1), a novel regulator of p53, enhances ferroptosis in glioblastoma.

BACKGROUND: Ferroptosis is an iron dependent cell death closely associated with p53 signaling pathway and is aberrantly regulated in glioblastoma (GBM), yet the underlying mechanism needs more exploration. Identifying new factors which regulate p53 and ferroptosis in GBM is essential for treatment. METHODS: Glioma cell growth was evaluated by cell viability assays and colony formation assays. Lipid reactive oxygen species (ROS) assays, lipid peroxidation assays, glutathione assays, and transmission electron microscopy were used to assess the degree of cellular lipid peroxidation of GBM. The mechanisms of RND1 in regulation of p53 signaling were analyzed by RT-PCR, western blot, immunostaining, co-immunoprecipitation, ubiquitination assays and luciferase reporter assays. The GBM-xenografted animal model was constructed and the tumor was captured by an In Vivo Imaging System (IVIS). RESULTS: From the The Cancer Genome Atlas (TCGA) database, we summarized that Rho family GTPase 1 (RND1) expression was downregulated in GBM and predicted a better prognosis of patients with GBM. We observed that RND1 influenced the glioma cell growth in a ferroptosis-dependent manner when GBM cell lines U87 and A172 were treated with Ferrostatin-1 or Erastin. Mechanistically, we found that RND1 interacted with p53 and led to the de-ubiquitination of p53 protein. Furthermore, the overexpression of RND1 promoted the activity of p53-SLC7A11 signaling pathway, therefore inducing the lipid peroxidation and ferroptosis of GBM. CONCLUSIONS: We found that RND1, a novel controller of p53 protein and a positive regulator of p53 signaling pathway, enhanced the ferroptosis in GBM. This study may shed light on the understanding of ferroptosis in GBM cells and provide new therapeutic ideas for GBM.

Development and Verification of Glutamatergic Synapse-Associated Prognosis Signature for Lower-Grade Gliomas.

Background: Lower-grade glioma (LGG) is the most common histology identified in gliomas, a heterogeneous tumor that may develop into high-grade malignant glioma that seriously shortens patient survival time. Recent studies reported that glutamatergic synapses might play an essential role in the progress of gliomas. However, the role of glutamatergic synapse-related biomarkers in LGG has not been systemically researched yet. Methods: The mRNA expression data of glioma and normal brain tissue were obtained from The Cancer Genome Atlas database and Genotype-Tissue Expression, respectively, and the Chinese Glioma Genome Atlas database was used as a validation set. Difference analysis was performed to evaluate the expression pattern of glutamatergic synapse-related genes (GSRGs) in LGG. The least absolute shrinkage and selection operator (LASSO) Cox regression was applied to construct the glutamatergic synapse-related risk signature (GSRS), and the risk score of each LGG sample was calculated based on the coefficients and expression value of selected GSRGs. Univariate and multivariate Cox regression analyses were used to investigate the prognostic value of risk score. Immunity profile and single-sample gene set enrichment analysis (ssGSEA) were performed to explore the association between risk score and the characters of tumor microenvironment in LGG. Gene set variation analysis (GSVA) was performed to investigate the potential pathways related to GSRS. The HPA database and real-time PCR were used to identify the expression of hub genes identified in GSRS. Results: A total of 22 genes of 39 GSRGs were found differentially expressed among normal and LGG samples. Through the LASSO algorithm, 14-genes GSRS constructed were associated with the prognosis and clinicopathological features of patients with LGG. Furthermore, the risk score level was significantly positively correlated with the infiltrating level of immunosuppressive cells, including M2 macrophages and regulatory T cells. GSVA identified a series of cancer-related pathways related to GSRS, such as P13K-AKT and P53 pathways. Moreover, ATAD1, NLGN2, OXTR, and TNR, hub genes identified in GSRS, were considered as potential prognostic biomarkers in LGG. Conclusion: A 14-genes GSRS was constructed and verified in this study. We provided a novel insight into the role of GSRS in LGG through a series of bioinformatics methods.

WAC, a novel GBM tumor suppressor, induces GBM cell apoptosis and promotes autophagy.

WAC is closely related to the occurrence and development of tumors. However, its role in human glioblastoma (GBM) and its potential regulatory mechanisms have not been investigated. This study demonstrated that WAC is downregulated in GBM, and its low expression predicts a poor prognosis. We investigated the effect of WAC on the proliferation of glioma cells through a CCK-8 assay, EdU incorporation, and cell formation. The effects of WAC on apoptosis and autophagy in glioma were determined by flow cytometry, TUNEL detection, immunofluorescence, q-PCR, WB, and scanning electron microscopy. We found that overexpression of WAC inhibited the proliferation of glioma cells, promoted apoptosis, and induced autophagy. Therefore, WAC is likely to play a role as a new regulatory molecule in glioma.

Notch intracellular domain regulates glioblastoma proliferation through the Notch1 signaling pathway.

Notch intracellular domain (NICD), also known as the activated form of Notch1 is closely associated with cell differentiation and tumor invasion. However, the role of NICD in glioblastoma (GBM) proliferation and the underlying regulatory mechanism remains unclear. The present study aimed to investigate the expression of NICD and Notch1 downstream gene HES5 in human GBM and normal brain samples and to further detect the effect of NICD on human GBM cell proliferation. For this purpose, western blotting and immunohistochemical staining were performed to analyze the expression of NICD in human GBM tissues, while western blotting and reverse-transcription quantitative PCR experiments were used to analyze the expression of Hes5 in human GBM tissues. A Flag-NICD vector was used to overexpress NICD in U87 cells and compound E and small interfering (si) Notch1 were used to downregulate NICD. Cellular proliferation curves were generated and BrdU assays performed to evaluate the proliferation of U87 cells. The results demonstrated that compared with normal brain tissues, the level of NICD protein in human GBM tissues was upregulated and the protein and mRNA levels of Hes5 were also upregulated in GBM tissues indicating that the Notch1 signaling pathway is activated in GBM. Overexpression of NICD promoted the proliferation of U87 cells in vitro while downregulation of NICD by treatment with compound E or siNotch1 suppressed the proliferation of U87 cells in vitro. In conclusion, NICD was upregulated in human GBM and NICD promoted GBM proliferation via the Notch1 signaling pathway. NICD may be a potential diagnostic marker and therapeutic target for GBM treatment.

Kiaa0101 serves as a prognostic marker and promotes invasion by regulating p38/snail1 pathway in glioma.

BACKGROUND: Kiaa0101, a regulator of cell proliferation, is overexpressed in many malignant tumors. However, its role in promoting invasion of glioma is poorly understood. Here, we investigated the effects of Kiaa0101 on glioma invasion and elucidated the underlying mechanisms of action. METHODS: We analyzed Kiaa0101 expression using datasets from four public databases, namely TCGA, CGGA, Gravendeel and Rembrandt as well as experimentally on 123 glioma samples via western blot (WB), RT-PCR and immunohistochemistry (IHC). We further quantified migration and invasion using wound healing and transwell assays. WB, IHC and immunofluorescence (IF) were used to detect expression of invasion related markers. Moreover, we detected tumor invasion of glioma cells in vivo in 5-week-old Balb/c nude mice. RESULTS: Kiaa0101 was upregulated in glioma, relative to non-tumor brain tissues, with the expression increasing with increase in glioma grade. Kiaa0101 mRNA expression was especially enriched in isocitrate dehydrogenase (IDH)1 wild-type glioma. Kaplan-Meier analysis, based on the aforementioned datasets, revealed that high Kiaa0101 levels were significantly associated with worse overall survival. Besides, shRNA-mediated Kiaa0101 knockdown inhibited migration and invasion of glioma cells by reducing snail1 expression both in vitro and in vivo, whereas its upregulation enhanced malignant behaviors of these cells. Furthermore, Kiaa0101 regulated snail1 expression by activating the p38MAPK signaling pathway. CONCLUSIONS: Our findings strongly indicate that Kiaa0101 is a prognostic biomarker for malignant tumors, and its inhibition may be an effective strategy for treating glioma.

Genetic deletion of Rnd3 suppresses apoptosis through NF­κB signaling in the brain.

Rho family GTPase 3 (RND3) is involved in multiple physiological activities involving the Rho kinase­dependent signaling pathway. The present study revealed a novel role of RND3 in the regulation of apoptosis in the brain. Using immunofluorescence and TUNEL assays, a decreased rate of brain apoptosis was observed in Rnd3­knockout mice. In addition, the function of RND3 in promoting apoptosis was determined in PC12 cells by immunoblotting assays and flow cytometry analysis in RNA interference and overexpression experiments. Furthermore, the present study demonstrated that Rnd3 and P65 protein interacted using immunoprecipitation analysis, and Rnd3 regulated apoptosis via its association with NF­κB P65. Notably, Rnd3 blocked the anti­apoptotic action of NF­κB P65 in vitro by downregulating P65. Therefore, RND3­NF­κB P65 represents a novel signaling pathway in the regulation of brain apoptosis. The present study suggested an alternative approach for the treatment of neurodegenerative diseases through regulation of apoptosis via the RND3­NF­κB P65 signaling pathway in the central nervous system.

RND2 attenuates apoptosis and autophagy in glioblastoma cells by targeting the p38 MAPK signalling pathway.

BACKGROUND: Inhibition of p38 MAPK signalling leads to glioblastoma multiform (GBM) tumourigenesis. Nevertheless, the molecular mechanism that induces p38 MAPK signalling pathway silencing during GBM genesis has yet to be determined. Identifying new factors that can regulate p38 MAPK signalling is important for tumour treatment. METHODS: Flow cytometry, TUNEL assays, immunofluorescence, JC-1 assays, and western blot analyses were used to detect the apoptosis of GBM cells. The specific methods used to detect autophagy levels in GBM cells were western blot analysis, LC3B protein immunofluorescence, LC3B puncta assays and transmission electron microscopy. The functions of these critical molecules were further confirmed in vivo by intracranial xenografts in nude mice. Tumour tissue samples and clinical information were used to identify the correlation between RND2 and p62 and LC3B expression, survival time of patients, and tumour volumes in clinical patients. RESULTS: By summarizing data from the TCGA database, we found that expression of the small GTPase RND2 was significantly increased in human glioblastomas. Our study demonstrated that RND2 functions as an endogenous repressor of the p38 MAPK phosphorylation complex. RND2 physically interacted with p38 and decreased p38 phosphorylation, thereby inhibiting p38 MAPK signalling activities. The forced expression of RND2 repressed p38 MAPK signalling, which inhibited glioblastoma cell autophagy and apoptosis in vitro and induced tumour growth in the xenografted mice in vivo. By contrast, the downregulation of RND2 enhanced p38 MAPK signalling activities and promoted glioma cell autophagy and apoptosis. The inhibition of p38 phosphorylation abolished RND2 deficiency-mediated GBM cell autophagy and apoptosis. Most importantly, our study found that RND2 expression was inversely correlated with patient survival time and was positively correlated with tumour size. CONCLUSIONS: Our findings revealed a new function for RND2 in GBM cell death and offered mechanistic insights into the inhibitory effects of RND2 with regard to the regulation of p38 MAPK activation.

Hypoxia induced ferritin light chain (FTL) promoted epithelia mesenchymal transition and chemoresistance of glioma.

BACKGROUND: Hypoxia, a fundamental characteristic of glioma, is considered to promote tumor malignancy by inducing process of epithelial mesenchymal transition (EMT). Ferritin Light Chain (FTL) is one of the iron metabolism regulators and is overexpressed in glioma. However, relationship between hypoxia and FTL expression and its role in regulating EMT remains unclear. METHODS: Immunohistochemistry (IHC), western blot and public datasets were used to evaluate FTL level in glioma. Wound healing, transwell assays, CCK8, annexin V staining assay were used to measure migration, invasion, proliferation and apoptosis of glioma cells in vitro. Interaction between HIF1A and FTL was assessed by luciferase reporter and Chromatin immunoprecipitation (ChIP) assays. Subcutaneous xenograft model was established to investigate in vivo growth. RESULTS: FTL expression was enriched in high grade glioma (HGG) and its expression significantly associated with IDH1/2 wildtype and unfavorable prognosis of glioma patients. FTL expression positively correlated with HIF1A in glioma tissues and obviously increased in U87 and U251 cells under hypoxia in a time-dependent manner. Mechanistically, HIF-1α regulates FTL expression by directly binding to HRE-3 in FTL promoter region. Furthermore, we found that knockdown FTL dramatically repressed EMT and reduced migration and invasion of glioma by regulating AKT/GSK3ß/ ß-catenin signaling both in vitro and in vivo. Moreover, our study found downregulation FTL decreased the survival rate and increased the apoptosis of glioma cells treated with temozolomide (TMZ). FTL expression segregated glioma patients who were treated with TMZ or with high MGMT promoter methylation into survival groups in TCGA dataset. Patients with methylated MGMT who had high FTL expression presented similar prognosis with patients with unmethylated MGMT. CONCLUSION: Our study strongly suggested that hypoxia-inducible FTL was a regulator of EMT and acted not only as a prognostic marker but also a novel biomarker of response to TMZ in glioma.

Small GTPase RHOE/RND3, a new critical regulator of NF-κB signalling in glioblastoma multiforme?

OBJECTIVES: Abnormal activation of NF-κB signalling is a major mechanism of apoptosis resistance in glioblastoma multiforme (GBM). Therefore, better understanding of the regulation of NF-κB signalling has a significant impact for GBM therapy. Here, we uncovered a critical role of the small GTPase RND3 in regulating the p65 subunit of NF-κB and NF-κB signalling in GBM. MATERIALS AND METHODS: Human GBM samples, GBM cells and a human orthotopic GBM-xenografted animal model were used. The mechanisms of RND3 in regulation of NF-κB signalling and GBM cell apoptosis were examined by luciferase assay, quantitative PCR, immunostaining, immunoblotting, immunofluorescence, coimmunoprecipitation, TUNEL staining, JC-1 analysis and flow cytometry. RESULTS: Overexpression of RND3 led to reduced p65 activity in GBM-cultured cells and a GBM animal model, indicating that the NF-κB pathway is negatively regulated by RND3 in GBM. Mechanistically, we found that RND3 bound p65 and promoted p65 ubiquitination, leading to decreased p65 protein levels. Furthermore, RND3 enhanced cleaved caspase 3 levels and promoted apoptosis in GBM cells, and RND3 expression was positively correlated with cleaved caspase 3 and IL-8 in human GBM samples. The effect of RND3 on promoting apoptosis disappeared when p65 ubiquitination was blocked by protease inhibitor carfilzomib or upon co-expression of ectopic p65. CONCLUSIONS: RND3 binds p65 protein and promotes its ubiquitination, resulting in reduced p65 protein expression and inhibition of NF-κB signalling to induce GBM cell apoptosis.

GOLM1 silencing inhibits the proliferation and motility of human glioblastoma cells via the Wnt/ß-catenin signaling pathway.

Golgi membrane protein 1 (GOLM1) is a type II transmembrane protein located in the cis- and medial-Golgi. Due to its function as an oncogene and proprotein convertase (PC) consensus site, GOLM1 will play a vital role in gene-targeted therapies and serve as a candidate tumor biomarker. However, few studies have explored its correlation with glioblastoma (GBM) progression. In this study, we detected the overexpression of the GOLM1 mRNA and protein in clinical GBM samples. The level of secreted GOLM1 in the serum from patients with GBM was also abnormally elevated, as determined by an Elisa. Then we utilized small interfering RNAs (siRNAs) to silence GOLM1 expression in GBM U87 and U251 cells. After silencing GOLM1 expression, the proliferation of cells decreased, the cell cycle was arrested in G1/S phase, and tumor cell motility was also inhibited. Moreover, the levels of proliferation-associated proteins and epithelial-mesenchymal transition (EMT)-related markers were also altered. Additionally, the Wnt/ß-catenin signaling pathway was significantly suppressed, particularly the nuclear translocation of ß-catenin. Knockdown of GOLM1 also inhibits xenograft tumor growth in nude mouse models.GOLM1 acts as a critical oncogene in GBM by promoting cell proliferation, migration and invasion. Its mechanism may be related to the Wnt/ß-catenin signaling pathway. GOLM1 also exhibits great potential as a biomarker for GBM.

Identification of differentially expressed key genes between glioblastoma and low-grade glioma by bioinformatics analysis.

Gliomas are a very diverse group of brain tumors that are most commonly primary tumor and difficult to cure in central nervous system. It's necessary to distinguish low-grade tumors from high-grade tumors by understanding the molecular basis of different grades of glioma, which is an important step in defining new biomarkers and therapeutic strategies. We have chosen the gene expression profile GSE52009 from gene expression omnibus (GEO) database to detect important differential genes. GSE52009 contains 120 samples, including 60 WHO II samples and 24 WHO IV samples that were selected in our analysis. We used the GEO2R tool to pick out differently expressed genes (DEGs) between low-grade glioma and high-grade glioma, and then we used the database for annotation, visualization and integrated discovery to perform gene ontology analysis and Kyoto encyclopedia of gene and genome pathway analysis. Furthermore, we used the Cytoscape search tool for the retrieval of interacting genes with molecular complex detection plug-in applied to achieve the visualization of protein-protein interaction (PPI). We selected 15 hub genes with higher degrees of connectivity, including tissue inhibitors metalloproteinases-1 and serum amyloid A1; additionally, we used GSE53733 containing 70 glioblastoma samples to conduct Gene Set Enrichment Analysis. In conclusion, our bioinformatics analysis showed that DEGs and hub genes may be defined as new biomarkers for diagnosis and for guiding the therapeutic strategies of glioblastoma.

PI3Kß inhibitor AZD6482 exerts antiproliferative activity and induces apoptosis in human glioblastoma cells.

Glioblastoma is the most common type of primary brain tumour in adults, and its pathogenesis is particularly complicated. Among the many possible mechanisms underlying its pathogenesis, hyperactivation of the PI3K/Akt pathway is essential to the occurrence and development of glioma through the loss of PTEN or somatic activating mutations in PIK3CA. In the present study, we investigated the effect of the PI3Kß inhibitor AZD6482 on glioma cells. The CCK-8 assay showed dose-dependent cytotoxicity in glioma cell lines treated with AZD6482. Additionally, AZD6482 treatment was found to significantly induce apoptosis and cell cycle arrest as detected using flow cytometry. Moreover, as shown using western blot analysis, the levels of p-AKT, p-GSK-3ß, Bcl-2, and cyclin D1 were decreased after AZD6482 treatment. In addition, we found that AZD6482 inhibited the migration and invasion of glioma cells as detected by wound healing and Transwell invasion assays. Taken together, our findings indicate that AZD6482 exerts an antitumour effect by inhibiting proliferation and inducing apoptosis in human glioma cells. AZD6482 may be applied as an adjuvant therapy to improve the therapeutic efficacy of glioblastoma treatment.

Identification of Core Biomarkers Associated with Outcome in Glioma: Evidence from Bioinformatics Analysis.

Glioma is the most common neoplasm of the central nervous system (CNS); the progression and outcomes of which are affected by a complicated network of genes and pathways. We chose a gene expression profile of GSE66354 from GEO database to search core biomarkers during the occurrence and development of glioma. A total of 149 samples, involving 136 glioma and 13 normal brain tissues, were enrolled in this article. 1980 differentially expressed genes (DEGs) including 697 upregulated genes and 1283 downregulated genes between glioma patients and healthy individuals were selected using GeoDiver and GEO2R tool. Then, gene ontology (GO) analysis as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were carried out using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Moreover, Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING) and Molecular Complex Detection (MCODE) plug-in was employed to imagine protein-protein interaction (PPI) of these DEGs. The upregulated genes were enriched in cell cycle, ECM-receptor interaction, and p53 signaling pathway, while the downregulated genes were enriched in retrograde endocannabinoid signaling, glutamatergic synapse, morphine addiction, GABAergic synapse, and calcium signaling pathway. Subsequently, 4 typical modules were discovered by the PPI network utilizing MCODE software. Besides, 15 hub genes were chosen according to the degree of connectivity, including TP53, CDK1, CCNB1, and CCNB2, the Kaplan-Meier analysis of which was further identified. In conclusion, this bioinformatics analysis indicated that DEGs and core genes, such as TP53, might influence the development of glioma, especially in tumor proliferation, which were expected to be promising biomarkers for diagnosis and treatment of glioma.

SSRP1 silencing inhibits the proliferation and malignancy of human glioma cells via the MAPK signaling pathway.

Structure-specific recognition protein 1 (SSRP1) has been considered as a potential biomarker, since aberrant high expression of SSRP1 has been detected in numerous malignant tumors. However, the correlation between the expression level of SSRP1 and glioma remains unclear. The present study attempted to investigate the role of SSRP1 in the pathogenesis of glioma. In the present study, our data revealed that SSRP1 overexpression was detected in glioma tissues at both the mRNA and protein levels using quantitative real-time RT-PCR and immunohistochemical analysis. We also demonstrated that the upregulated expression of SSRP1 was correlated with the World Health Organization (WHO) grade of glioma. The knockdown of SSRP1 by siRNA not only resulted in the inhibition of cell proliferation, but also significantly inhibited glioma cell migration and invasion. Mechanistic analyses revealed that SSRP1 depletion suppressed the activity of the phosphorylation of the MAPK signaling pathway. In conclusion, the present study indicated that SSRP1 regulated the proliferation and metastasis of glioma cells via the MAPK signaling pathway.

TGX-221 inhibits proliferation and induces apoptosis in human glioblastoma cells.

Glioblastoma is the most common type of primary brain tumor in adults, with high mortality and morbidity rates. More effective therapeutic strategies are imperative. Previous studies have shown that the known p110-ß-selective inhibitor TGX-221 blocks the activation of PKB/Akt in PTEN-deficient cells. We treated U87 and U251 glioblastoma cells with TGX-221 to determine the effect of TGX-221. We performed a Cell Counting Kit-8 (CCK-8) test, EDU staining and cell cycle distribution analysis and found that TGX-221 inhibited glioblastoma cell proliferation. Next, the effect of TGX-221 on cell apoptosis was investigated using flow cytometry. These results demonstrated that TGX-221 induced apoptosis in glioblastoma cells. Moreover, migration and invasion assays revealed that TGX-221 inhibited human glioblastoma cell migration and invasion. Collectively, our study revealed that TGX-221 could inhibit proliferation and induce apoptosis in glioblastoma cells.