Knockdown of lncRNA GHET1 inhibits osteosarcoma cells proliferation, invasion, migration and EMT in vitro and in vivo

2018 ◽  
Vol 23 (4) ◽  
pp. 589-601 ◽  
Author(s):  
Wei Yang ◽  
Zhiming Shan ◽  
Xinfang Zhou ◽  
Liangqun Peng ◽  
Chongyang Zhi ◽  
...  
Keyword(s):  
Osteosarcoma Cells

scholarly journals Targeting autophagy enhances atezolizumab-induced mitochondria-related apoptosis in osteosarcoma

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Zhuochao Liu ◽  
Hongyi Wang ◽  
Chuanzhen Hu ◽  
Chuanlong Wu ◽  
Jun Wang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Antitumor Immunity ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Specific Monoclonal Antibody ◽  
Osteosarcoma Cells ◽  
Jnk Pathway ◽  
In Vivo Experiments

AbstractIn this study, we identified the multifaceted effects of atezolizumab, a specific monoclonal antibody against PD-L1, in tumor suppression except for restoring antitumor immunity, and investigated the promising ways to improve its efficacy. Atezolizumab could inhibit the proliferation and induce immune-independent apoptosis of osteosarcoma cells. With further exploration, we found that atezolizumab could impair mitochondria of osteosarcoma cells, resulting in increased release of reactive oxygen species and cytochrome-c, eventually leading to mitochondrial-related apoptosis via activating JNK pathway. Nevertheless, the excessive release of reactive oxygen species also activated the protective autophagy of osteosarcoma cells. Therefore, when we combined atezolizumab with autophagy inhibitors, the cytotoxic effect of atezolizumab on osteosarcoma cells was significantly enhanced in vitro. Further in vivo experiments also confirmed that atezolizumab combined with chloroquine achieved the most significant antitumor effect. Taken together, our study indicates that atezolizumab can induce mitochondrial-related apoptosis and protective autophagy independently of the immune system, and targeting autophagy is a promising combinatorial approach to amplify its cytotoxicity.

scholarly journals LncRNA SNHG15 contributes to doxorubicin resistance of osteosarcoma cells through targeting the miR-381-3p/GFRA1 axis

2020 ◽  
Vol 15 (1) ◽  
pp. 871-883
Author(s):  
Jinshan Zhang ◽  
Dan Rao ◽  
Haibo Ma ◽  
Defeng Kong ◽  
Xiaoming Xu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Noncoding Rna ◽  
Xenograft Model ◽  
Inhibitory Effect ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells

AbstractBackgroundOsteosarcoma is a common primary malignant bone cancer. Long noncoding RNA small nucleolar RNA host gene 15 (SNHG15) has been reported to play an oncogenic role in many cancers. Nevertheless, the role of SNHG15 in the doxorubicin (DXR) resistance of osteosarcoma cells has not been fully addressed.MethodsCell Counting Kit-8 assay was conducted to measure the half-maximal inhibitory concentration value of DXR in osteosarcoma cells. Western blotting was carried out to examine the levels of autophagy-related proteins and GDNF family receptor alpha-1 (GFRA1). Quantitative reverse transcription-polymerase chain reaction was performed to determine the levels of SNHG15, miR-381-3p, and GFRA1. The proliferation of osteosarcoma cells was measured by MTT assay. The binding sites between miR-381-3p and SNHG15 or GFRA1 were predicted by Starbase bioinformatics software, and the interaction was confirmed by dual-luciferase reporter assay. Murine xenograft model was established to validate the function of SNHG15 in vivo.ResultsAutophagy inhibitor 3-methyladenine sensitized DXR-resistant osteosarcoma cell lines to DXR. SNHG15 was upregulated in DXR-resistant osteosarcoma tissues and cell lines. SNHG15 knockdown inhibited the proliferation, DXR resistance, and autophagy of osteosarcoma cells. MiR-381-3p was a direct target of SNHG15, and GFRA1 bound to miR-381-3p in osteosarcoma cells. SNHG15 contributed to DXR resistance through the miR-381-3p/GFRA1 axis in vitro. SNHG15 depletion contributed to the inhibitory effect of DXR on osteosarcoma tumor growth through the miR-381-3p/GFRA1 axis in vivo.ConclusionsSNHG15 enhanced the DXR resistance of osteosarcoma cells through elevating the autophagy via targeting the miR-381-3p/GFRA1 axis. Restoration of miR-381-3p expression might be an underlying therapeutic strategy to overcome the DXR resistance of osteosarcoma.

scholarly journals Tumor Suppressor Function of miR-127-3p and miR-376a-3p in Osteosarcoma Cells

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2019 ◽  
Author(s):  
Joerg Fellenberg ◽  
Burkhard Lehner ◽  
Heiner Saehr ◽  
Astrid Schenker ◽  
Pierre Kunz
Keyword(s):  
Tumor Suppressor ◽  
Therapeutic Strategies ◽  
High Dose ◽  
Osteosarcoma Cell ◽  
Tumor Suppressor Function ◽  
Osteosarcoma Cells ◽  
Aberrant Expression ◽  
Suppressor Function

Since the introduction of high-dose chemotherapy about 35 years ago, survival rates of osteosarcoma patients have not been significantly improved. New therapeutic strategies replacing or complementing conventional chemotherapy are therefore urgently required. MicroRNAs represent promising targets for such new therapies, as they are involved in the pathology of multiple types of cancer, and aberrant expression of several miRNAs has already been shown in osteosarcoma. In this study, we identified silencing of miR-127-3p and miR-376a-3p in osteosarcoma cell lines and tissues and investigated their role as potential tumor suppressors in vitro and in vivo. Transfection of osteosarcoma cells (n = 6) with miR-127-3p and miR-376a-3p mimics significantly inhibited proliferation and reduced the colony formation capacity of these cells. In contrast, we could not detect any influence of miRNA restoration on cell cycle and apoptosis induction. The effects of candidate miRNA restoration on tumor engraftment and growth in vivo were analyzed using a chicken chorioallantoic membrane (CAM) assay. Cells transfected with mir-127-3p and miR-376a-3p showed reduced tumor take rates and tumor volumes and a significant decrease of the cumulative tumor volumes to 41% and 54% compared to wildtype cells. The observed tumor suppressor function of both analyzed miRNAs indicates these miRNAs as potentially valuable targets for the development of new therapeutic strategies for the treatment of osteosarcoma.

scholarly journals HDAC6 inhibitor WT161 performs antitumor effect on osteosarcoma and synergistically interacts with 5-FU

2021 ◽  
Author(s):  
Jun Sun ◽  
Wei Wu ◽  
Xiaofeng Tang ◽  
Feifei Zhang ◽  
Cheng Ju ◽  
...  
Keyword(s):  
Dependent Manner ◽  
Osteosarcoma Cells ◽  
Synergistic Inhibition ◽  
Proliferative Effect ◽  
Xenograft Models ◽  
Hdac6 Inhibitor ◽  
Underlying Mechanisms ◽  
Induced Apoptosis

Background: WT161, as a selective HDAC6 inhibitor, has been shown to play anti-tumor effects on several kinds of cancers. The aim of this study is to explore the roles of WT161 in osteosarcoma and its underlying mechanisms. Methods: The anti-proliferative effect of WT161 on osteosarcoma cells was examined using MTT assay and colony formation assay. Cell apoptosis was analyzed using flow cytometer. The synergistic effect was evaluated by isobologram analysis using CompuSyn software. The osteosarcoma xenograft models were established to evaluate the anti-proliferative effect of WT161 in vivo. Results: WT161 suppressed the cell growth and induced apoptosis of osteosarcoma cells in a dose- and time-dependent manner. Mechanistically, we found that WT161 treatment obviously increased the protein level of PTEN and decreased the phosphorylation level of AKT. More importantly, WT161 show synergistic inhibition with 5-FU on osteosarcoma cells in vitro and in vivo. Conclusions: These results indicate that WT161 inhibits the growth of osteosarcoma through PTEN and has a synergistic efficiency with 5-FU.

Muramyl Peptides Augment the In Vitro and In Vivo Cytostatic Activity of Canine Plastic-Adherent Mononuclear Cells Against Canine Osteosarcoma Cells

1993 ◽  
Vol 8 (2) ◽  
pp. 137-144 ◽  
Author(s):  
Bernard W. Smith ◽  
Ilene D. Kurzman ◽  
Kevin T. Schultz ◽  
Charles J. Czuprynski ◽  
E. Gregory MacEwen
Keyword(s):  
Mononuclear Cells ◽  
Cytostatic Activity ◽  
Osteosarcoma Cells ◽  
Canine Osteosarcoma

scholarly journals MiR-92a Inhibits the Progress of Osteosarcoma Cells and Increases the Cisplatin Sensitivity by Targeting Notch1

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Quanxiang Liu ◽  
Yang Song ◽  
Xianliang Duan ◽  
Yuan Chang ◽  
Jianping Guo
Keyword(s):  
Cell Cycle ◽  
Annexin V ◽  
Osteosarcoma Cells ◽  
Transwell Assay ◽  
Diphenyltetrazolium Bromide ◽  
Cisplatin Sensitivity ◽  
Novel Strategy

Background. MicroRNAs (miRs) have been implicated in the development and progression of osteosarcoma. Here, we aimed to illustrate the important role of miR-92a on the regulation of OS development which may help to establish a novel strategy for OS diagnosis and treatment. Materials and Methods. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle and apoptosis were assessed by flow cytometry with PI and PI/Annexin-V stain, respectively. The expression of proteins was examined by western blot. qPCR was used to detect the expression of RNA. Cell migration was assayed with transwell assay. Results. MiR-92a inhibited the proliferation and the migration of OS in vitro and reduced the volume of the tumour in vivo. Further, miR-92a enhanced cisplatin sensitivity of OS. MiR-92a directly targeted Notch1. Conclusion. Together, our results indicate that miR-92a inhibited cell growth, migration, and enhanced cisplatin sensitivity of OS cell by targeting Notch1.

scholarly journals Tanshinone IIA induces intrinsic apoptosis in osteosarcoma cells both in vivo and in vitro associated with mitochondrial dysfunction

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Sheng-Teng Huang ◽  
Chao-Chun Huang ◽  
Wen-Liang Huang ◽  
Tsu-Kung Lin ◽  
Pei-Lin Liao ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Tanshinone Iia ◽  
Intrinsic Apoptosis ◽  
Osteosarcoma Cells
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