BackgroundMalignant glioma is the most devastating and aggressive tumour in the brain and is characterised by high morbidity, high mortality and extremely poor prognosis. The main purpose of the present study was to investigate the effects of schisandrin B (Sch B) on glioma cells both in vitro and in vivo and to explore the possible anticancer mechanism underlying Sch B-induced apoptosis and cell cycle arrest.MethodsThe anti-proliferative ability of Sch B on glioma cells were assessed by MTT and clony formation assays. Flow cytometric analysis was used to detect cell cycle changes. Apoptosis was determined by Hoechst 33342 staining and annexin V/PI double-staining assays. The mitochondrial membrane potential was detected by Rhodamine 123 staining. The in vivo efficacy of Sch B was measured using a U87 xenograft model in nude mice. The expressions of the apoptosis-related and cell cycle-related proteins were analysed by western blot. Student’s t-test was used to compare differences between treated groups and their controls.ResultsWe found that Sch B inhibited growth in a dose- and time-dependent manner as assessed by MTT assay. In U87 and U251 cells, the number of clones was strongly suppressed by Sch B. Flow cytometric analysis revealed that Sch B induced cell cycle arrest in glioma cells at the G0/G1 phase. In addition, Sch B induced glioma cell apoptosis and reduced mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Mechanically, western blot analysis indicated that Sch B induced apoptosis by caspase-3, caspase-9, PARP, and Bcl-2 activation. Moreover, Sch B significantly inhibited tumour growth in vivo following the subcutaneous inoculation of U87 cells in athymic nude mice.CoclusionsIn summary, Sch B can reduce cell proliferation and induce apoptosis in glioma cells and has potential as a novel anti-tumour therapy to treat gliomas.

Insights into the roles of microR NAs (miRNAs/miRs) in development and disease, particularly in cancer, have made miRNAs attractive tools and targets for novel therapeutic approaches in the treatment of glioma. miR-34a, as a well-known tumor suppressor miRNA, is closely related with cellular senescence. Mesenchymal stem cells (MSCs) are a major component of the tumor microenvironment and possess the ability to deliver exogenous miRs to glioma cells to exert anti-tumor effects. The present study investigated whether modified MSCs with miR-34a possess an anti-tumor function in glioma cells. A Transwell system was used to co-culture U87 glioma cells and MSCs overexpressing miR-34a, and cell proliferation and senescence assessed. The expression of senescence-related genes p53, Cdkn1a, and Cdkn2c were tested using reverse transcription-quantitative polymerase chain reaction and protein expression levels of sirtuin 1 (SIRT1) and γ-H2A histone family, member X were detected by western blotting. Telomerase activity of U87 cells was examined using the Telo TAGGG Telomerase PCR ELISA PLUS kit. The results demonstrated that the delivered exogenous miR-34a from MSCs significantly decreased expression of the target gene SIRT1. In addition, the delivered miR-34a decreased the proliferation of glioma cells and provoked the expression of senescence-related genes p53, Cdkn1a, and Cdkn2c. In addition, upregulation of miR-34a induced DNA damage, shortened telomere length and impaired telomerase activity. However, these pro-senescent effects were reversed by forced SIRT1 upregulation. In conclusion, the results demonstrated a novel role for miR-34a, inducing glioma cell senescence, whereas miR-34a modulation of SIRT1, inducing DNA damage, is crucial for miRNA replacement therapy in glioma treatment.

Brusatol (Bru), a Chinese herbal extract, has a variety of anti-tumor effects. However, little is known regarding its role and underlying mechanism in glioblastoma cells. Here, we found that Bru could inhibit the proliferation of glioblastoma cells in vivo and in vitro. Besides, it also had an inhibitory effect on human primary glioblastoma cells. RNA-seq analysis indicated that Bru possibly achieved these effects through inhibiting the expression of extracellular matrix protein 1 (ECM1). Down-regulating the expression of ECM1 via transfecting siRNA could weaken the proliferation and invasion of glioblastoma cells and promote the inhibitory effect of Bru treatment. Lentivirus-mediated overexpression of ECM1 could effectively reverse this weakening effect. Our findings indicated that Bru could inhibit the proliferation and invasion of glioblastoma cells by suppressing the expression of ECM1, and Bru might be a novel effective anticancer drug for glioblastoma cells.

Abstract. Heat shock protein 47 (HSP47) is a 47 kDa collagen binding protein that has a close relationship with the development and progression of tumours. However, little is known concerning the expression profile of HSP47 in laryngeal squamous cell carcinoma (LSCC) patients and there is still insufficient data concerning the underlying mechanisms. The aim of the present study was to explore the expression of HSP47 in LSCC and provide an overview of its association with tumourigenicity and clinical prognosis. The expression of HSP47 in LSCC and adjacent non-cancerous laryngeal tissues was assessed via western blotting and immunohistochemical studies. The prognostic significance of HSP47 expression was analysed using a Kaplan-Meier survival curve. To investigate the influence of HSP47 on the viability, invasion and apoptosis of a LSCC cell line, we performed an in vitro analysis with plasmid vectors and small interfering RNA (siRNA). Our results showed that HSP47 protein expression in the LSCC tissues was markedly decreased compared to that noted in the adjacent non-cancerous tissues, and low expression of HSP47 was correlated with poor prognosis in LSCC patients. Upregulation of HSP47 via plasmid vectors inhibited the proliferation, reduced the invasive ability, increased the sensitivity to cisplatin chemotherapy, promoted apoptosis, and induced the G1 phase arrest of LSCC cells in vitro. The expression of apoptosis-regulating proteins was also altered when HSP47 was upregulated, involving increased expression of cleaved caspase-7/-8/-9, PARP, and Bax and decreased expression of Bcl-2. Our present data suggest that HSP47 is an important prognostic factor and an attractive therapeutic target in LSCC due to its influence on the biological behaviour of LSCC cells.

Glioma is an extremely aggressive and lethal type of brain tumour that originates from glial cells. MicroRNA (miRNA) dysregulation has been implicated in the occurrence and progression of many human cancers, including glioma. Thus, some specific miRNAs are potential therapeutic targets for glioma diagnosis, therapy and prognosis. MicroRNA-342 (miR‑342) has been reported to be abnormally expressed in various types of cancer. However, the precise roles of miR‑342 in glioma remain unknown. The present study showed that miR‑342 is relatively downregulated in glioma tissues and cell lines compared with that in adjacent normal tissues and normal human astrocytes. We observed that low miR‑342 expression levels are correlated with advanced WHO grades and low KPS scores of glioma patients. In addition, the results of the functional assays demonstrated that miR‑342 overexpression inhibits the proliferation and invasion of glioma cells and induces apoptosis. Further investigation revealed that P21 activated kinases 4 (PAK4) is a direct target of miR‑342 in glioma. PAK4 was significantly upregulated in glioma tissues and inversely correlated with miR‑342 expression. Moreover, PAK4 knockdown can mimic the effects of miR‑342 on glioma cell proliferation, invasion and apoptosis. Notably, restoration of expression of PAK4 reversed the suppressive effects induced by the miR‑342 in the glioma cells. The upregulation of miR‑342 inactivated the AKT and ERK pathways in glioma. These findings may contribute to the understanding of the molecular mechanism underlying the carcinogenesis and progression of glioma, and to provide novel therapeutic target for the treatment of glioma patients.