ABSTRACT
Heterostructured materials have great potential as cathodes for zinc-ion batteries (ZIBs) because of their fast Zn2+ transport channels. Herein, hollow MoS2@C@Cu2S heterostructures are innovatively constructed using a template-engaged method. The carbon layer improves the electrical conductivity, provides a high in situ growth area, and effectively restricts volume expansion during the recycling process. MoS2 nanosheets are grown on the surfaces of hollow C@Cu2S nanocubes using the in situ template method, further expanding the specific surface area and exposing more active sites to enhance the electrical conductivity. As expected, an admirable reversible capacity of 197.2 mA h g-1 can be maintained after 1000 cycles with a coulombic efficiency of 91.1%. Therefore, we firmly believe that this work points the way forward for high-performance materials design and energy storage systems.
ABSTRACT
Cisplatin, as a first-line chemotherapy drug, has been widely applied for therapy of osteosarcoma. However, its application is limited by drug resistance and serious side effects, including nephrotoxicity and ototoxicity. Suberoylanilide hydroxamic acid (SAHA) is a newly developed histone deacetylase (HDAC) inhibitor, which is the first Food and Drug Administration-approved HDAC inhibitor for the treatment of cutaneous manifestations of T-cell lymphoma. However, SAHA as a monotherapy was revealed to be limited, particularly in solid tumors. In the present study, 143B osteosarcoma cells were treated with multiple concentrations of SAHA or cisplatin, either alone or combined. The morphological characteristics of the treated cells were observed using an inverted microscope. The cytotoxicity effects of the combination of SAHA and cisplatin on 143B cells were analyzed by MTT assay, colony formation assay, wound healing cell migration assay, cell apoptosis assay and cell cycle analysis. Western blot analysis was performed to detect the protein expression levels of B cell lymphoma-2 (Bcl-2)-associated X protein (Bax), Bcl-2, cleaved-caspase-3, cleaved-caspase-8 and cleaved-poly (ADP-ribose) polymerase (PARP). The experimental data indicated that the inhibition of cell proliferation in the combination group was significantly increased compared with that in single drug groups. Expression levels of pro-apoptotic protein were upregulated, whereas anti-apoptotic Bcl-2 was downregulated significantly in 143B cells following SAHA/cisplatin treatment. Taken together, the results revealed that the combination of SAHA and cisplatin inhibited the proliferation of 143B cells and induced their apoptosis synergistically, and this effectiveness may be mediated by caspase activation.
ABSTRACT
Osteosarcoma (OS) is the most common bone tumor characterized with a high risk of amputation and malignant morbidity among teenagers and adolescents. However, relevant pathogenic/biological mechanisms underlying OS-genesis remains to be ambiguous. The aim of this study was to elucidate functional relationship about microRNAs-mRNAs networks and to identify potential molecular markers via a computational method. Gene expression profile (GSE70415) was recruited from Gene Expression Omnibus. 3856 differentially expressed genes and 250 significantly expressed microRNAs were identified by using GCBI. The results of GO and KEGG pathways associated proteomics analysis indicated that extracellular matrix organization, small molecule metabolic process, cell adhesion (GO IDs: 0030198, 0044281, 0007155) and pathways in cancer, PI3K-Akt signaling pathway, metabolic pathways (pathway IDs: 5200, 4151, 1100) were significantly enriched. In addition, CKMT2, miR-93b-5p, miR-29b-3p were found to be positively/negatively correlated with TP53, EGFR, and MMP members mediated OS development, including angiogenesis, migration and invasion. Further visualization of collective effect of 1181 microRNAs-mRNAs pairs and protein-protein interactions was realized by applying with cytosacpe. In summary, our work provided a better understanding of non-coding regulatory mechanisms of transcriptomics and unraveled essential molecular biomarkers in osteosarcoma.
Subject(s)
Bone Neoplasms/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Neoplasm Proteins/genetics , Osteosarcoma/genetics , Adolescent , Bone Neoplasms/diagnosis , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Creatine Kinase/genetics , Creatine Kinase/metabolism , Creatine Kinase, Mitochondrial Form , Databases, Genetic , ErbB Receptors/genetics , ErbB Receptors/metabolism , Female , Gene Expression Profiling , Gene Ontology , Gene Regulatory Networks , Humans , Male , Matrix Metalloproteinases/genetics , Matrix Metalloproteinases/metabolism , MicroRNAs/metabolism , Molecular Sequence Annotation , Neoplasm Proteins/metabolism , Osteosarcoma/diagnosis , Osteosarcoma/metabolism , Osteosarcoma/pathology , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Protein Interaction Mapping , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Neoplasm/genetics , RNA, Neoplasm/metabolism , Signal Transduction , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolismABSTRACT
The nephroblastoma overexpressed (NOV) gene, a member of the CCN gene family that encodes secreted proteins involved in a variety of processes including tumorigenesis, is often altered in a variety of tumors, including osteosarcoma. Recent studies indicated that NOV promotes osteosarcoma metastasis, but its biological functions and molecular mechanisms on osteosarcoma proliferation have yet to be fully elucidated. The aim of the present study was to examine the role of NOV in osteosarcoma biology. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis were performed to characterize the endogenous expression of NOV in osteosarcoma cell lines. Recombinant adenovirus expressing NOV/siNOV (AdNOV/AdsiNOV) was used to infect osteosarcoma cell lines with a relatively low/high endogenous NOV expression to determine the functional relevance of NOV expression to osteosarcoma cell growth and migration in vitro, respectively. As a result, osteosarcoma cell proliferation was significantly reduced by NOV upregulation, indicated by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltrazolium bromide (MTT), colony forming assay and cell cycle analysis. Cell apoptosis was markedly induced, as indicated by Hoechst 33258 staining assay and flow cytometry (FCM) detection. Despite the antiproliferative effect, NOV-transfected osteosarcoma cells exhibited increased migration ability. The possible molecular mechanisms underlying the biological role of NOV were also investigated. The results demonstrated that NOV increased the phosphorylation of p38 and c-Jun N-terminal kinase (JNK) mitogen-actived protein kinases (MAPKs) in osteosarcoma cell lines. When the phosphorylation of p38 and JNK were inhibited by SB203580 (p38 inhibitor) or SP600125 (JNK inhibitor), respectively, the NOV-induced proliferation inhibition and cell apoptosis were reversed. In conclusion, the results revealed that NOV regulates the tumor growth of osteosarcoma cells through activation of the MAPK signaling pathway and promotes osteosarcoma cell migration in vitro.
