scholarly journals Knockdown of Long Noncoding RNA ENST457720 Inhibits Proliferation of Non-Small Cell Lung Cancer Cells In Vitro and In Vivo

2018 ◽  
Vol 27 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Jia Yu ◽  
Qiyu Fang ◽  
Shuyan Meng
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Noncoding Rna ◽  
Biological Significance ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Non-small cell lung cancer (NSCLC) represents the leading cause of cancer-related mortality worldwide. More and more reports have identified important roles for long noncoding RNAs (lncRNAs) in cancer development. ENST457720 expression was upregulated in lung adenocarcinoma in a microarray-based lncRNA screen. We determined the expression levels of ENST457720 in NSCLC tissues with quantitative real-time PCR and then studied their clinical significance. We explored the biological significance of ENST457720 with gain- and loss-of-function analyses in vitro and in vivo. In this study, ENST457720 was expressed at higher levels in NSCLC tissues than in paired normal tissues. Higher ENST457720 expression was associated with larger tumor sizes, lymph node metastasis, and advanced TNM stage. ENST457720 silencing suppressed NSCLC cell proliferation in vitro and in vivo. Moreover, ENST457720 knockdown inhibited NSCLC invasion and reversed the epithelial-to-mesenchymal transition. ENST457720 promoted NSCLC proliferation and invasion, which may be a novel potential therapeutic target for NSCLC.

scholarly journals Baicalein Inhibits Orthotopic Human Non-Small Cell Lung Cancer Xenografts via Src/Id1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Zhengxiao Zhao ◽  
Baojun Liu ◽  
Jing Sun ◽  
Linwei Lu ◽  
Lumei Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Non-small cell lung cancer (NSCLC) is one of the most lethal cancers worldwide. Inhibitor of differentiation 1 (Id1) is the member mostly linked to tumorigenesis in Id family and a potential molecular target in cancer therapy. In the current study, we established an orthotopic lung cancer model by injecting athymic nude mice with A549 cells and evaluated the antitumor effect of baicalein and expression of Id1-related proteins in vivo and in vitro. Micro-CT images showed that tumor volume in baicalein group was significantly reduced. Western blot analysis revealed that baicalein suppressed the expression of Id1 protein, epithelial-to-mesenchymal transition (EMT) related molecules (N-Cadherin, vimentin), and angiogenesis related protein (VEGF-A), accompanied by upregulation of epithelial markers (such as E-cadherin). In addition, phosphorylation of upstream molecular Src was significantly restrained after baicalein treatment. This study firstly demonstrates that baicalein inhibits tumor growth in orthotopic human NSCLC xenografts via targeting Src/Id1 pathway.

scholarly journals Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Jianjiao Ni ◽  
Xiaofei Zhang ◽  
Juan Li ◽  
Zhiqin Zheng ◽  
Junhua Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Osteoclast Differentiation ◽  
Small Cell ◽  
Signalling Pathway ◽  
Small Cell Lung

AbstractBone is a frequent metastatic site of non-small cell lung cancer (NSCLC), and bone metastasis (BoM) presents significant challenges for patient survival and quality of life. Osteolytic BoM is characterised by aberrant differentiation and malfunction of osteoclasts through modulation of the TGF-β/pTHrP/RANKL signalling pathway, but its upstream regulatory mechanism is unclear. In this study, we found that lncRNA-SOX2OT was highly accumulated in exosomes derived from the peripheral blood of NSCLC patients with BoM and that patients with higher expression of exosomal lncRNA-SOX2OT had significantly shorter overall survival. Additionally, exosomal lncRNA-SOX2OT derived from NSCLC cells promoted cell invasion and migration in vitro, as well as BoM in vivo. Mechanistically, we discovered that NSCLC cell-derived exosomal lncRNA-SOX2OT modulated osteoclast differentiation and stimulated BoM by targeting the miRNA-194-5p/RAC1 signalling axis and TGF-β/pTHrP/RANKL signalling pathway in osteoclasts. In conclusion, exosomal lncRNA-SOX2OT plays a crucial role in promoting BoM and may serve as a promising prognostic biomarker and treatment target in metastatic NSCLC.

scholarly journals Docetaxel-loaded exosomes for targeting non-small cell lung cancer: preparation and evaluation in vitro and in vivo

Drug Delivery ◽  
2021 ◽  
Vol 28 (1) ◽  
pp. 1510-1523
Author(s):  
Ying Wang ◽  
Mimi Guo ◽  
Dingmei Lin ◽  
Dajun Liang ◽  
Ling Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Preparation And Evaluation

scholarly journals Upregulation of IL-11, an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer

2018 ◽  
Vol 45 (6) ◽  
pp. 2213-2224 ◽  
Author(s):  
Meng Zhao ◽  
Yahui Liu ◽  
Ran Liu ◽  
Jin Qi ◽  
Yongwang Hou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Background/Aims: Cytokines are key players in tumorigenesis and are potential targets in cancer treatment. Although IL-6 has attracted considerable attention, interleukin 11 (IL-11), another member of the IL-6 family, has long been overlooked, and little is known regarding its specific function in non-small cell lung cancer (NSCLC). In this study, we explored IL-11’s role in NSCLC and the detailed mechanism behind it. Methods: Cell proliferation in response to IL-11 was determined by colony formation, BrdU incorporation and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Cell motility was measured by Transwell and wound healing assays. NSCLC xenograft models were used to confirm oncogenic function of IL-11 in vivo. Immunohistochemical staining and western blot assay were performed to detect epithelial–mesenchymal transition (EMT) markers and cell signaling pathway alterations. Eighteen NSCLC patients and 5 normal lung samples were collected together with data from an online database to determine the link between IL-11 expression and malignant progression. Results: We observed that IL-11 was upregulated in NSCLC samples compared with normal tissue samples and correlated with poor prognosis. Data from in vitro and in vivo models indicated that IL-11 promotes cell proliferation and tumorigenesis. Cell migration and invasion were also enhanced by IL-11. Epithelial–mesenchymal transition (EMT) was also observed after IL-11 incubation. Furthermore, IL-11 activated AKT and STAT3 in our experimental models. In addition, we observed that hypoxia induced IL-11 expression in NSCLC cells. Deferoxamine (DFX) or dimethyloxalylglycine (DMOG) induced hypoxia-inducible factor 1-alpha (HIF1α) upregulation, which enhanced IL-11 expression in NSCLC cells. Conclusions: Taken together, our results indicate that IL-11 is an oncogene in NSCLC, and elucidating the mechanism behind it may provide insights for NSCLC treatment.

scholarly journals Arsenic sulfide reverses cisplatin resistance in non‐small cell lung cancer in vitro and in vivo through targeting PD‐L1

2021 ◽  
Vol 12 (19) ◽  
pp. 2551-2563
Author(s):  
Wei Tian ◽  
Yinping Sun ◽  
Yuping Cheng ◽  
Xiao Ma ◽  
Weina Du ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cisplatin Resistance ◽  
Small Cell ◽  
Arsenic Sulfide ◽  
Small Cell Lung

scholarly journals Sinoporphyrin Sodium-Mediated Sonodynamic Therapy Inhibits RIP3 Expression and Induces Apoptosis in the H446 Small Cell Lung Cancer Cell Line

2018 ◽  
Vol 51 (6) ◽  
pp. 2938-2954 ◽  
Author(s):  
Jing Shen ◽  
Shoubo Cao ◽  
Xin Sun ◽  
Bo Pan ◽  
Jingyan Cao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Line ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Cell Counting ◽  
Small Cell Lung ◽  
Sonodynamic Therapy

Background/Aims: Sonodynamic therapy (SDT) is expected to be a new method to solve the clinical problems caused by advanced metastasis in patients with lung cancer. The use of ultrasound has the advantage of being noninvasive, with deep-penetration properties. This study explored the anti-tumor effect of SDT with a new sonosensitizer, sinoporphyrin sodium (DVDMS), on the human small cell lung cancer H446 cell line in vitro and in vivo. Methods: Absorption of DVDMS was detected by a fluorescence spectrophotometer, and DVDMS toxicity was determined using a Cell Counting Kit-8. Mitochondrial membrane potential (MMP) was assessed using the JC-1 fluorescent probe. Cell apoptosis was measured by flow cytometry, and apoptosis-related proteins were detected by western blotting. The expression of cytokines was measured using an enzyme-linked immunosorbent assay and quantitative real-time PCR. To verify the in vitro results, we detected tumor volumes and weight changes in a xenograft nude mouse model after DVDMS-SDT. Hematoxylin and eosin staining was used to observe changes to the tumor, heart, liver, spleen, lung, and kidney of the mice, and immunohistochemistry was used to examine changes in the expression of tumor CD34 and receptor-interacting protein kinase-3 (RIP3), while terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to observe apoptosis in tumor tissues. Results: DVDMS-SDT-treated H446 cells increased the rate of cellular apoptosis and the levels of reactive oxygen species (ROS), cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, and caspase-10, and decreased the levels of MMP, RIP3, B-cell lymphoma 2, vascular endothelial growth factor, and tumor necrosis factor-α. The sonotoxic effect was mediated by ROS and was reduced by a ROS scavenger (N-acetyl-L-cysteine). In the in vivo mouse xenograft model, DVDMS-SDT showed efficient anti-cancer effects with no visible side effects. Conclusion: DVDMS-SDT induced apoptosis in H446 cells, in part by targeting mitochondria through the mitochondria-mediated apoptosis signaling pathway, and the extrinsic apoptosis pathway was also shown to be involved. Both apoptosis and changes in RIP3 expression were closely related to the generation of ROS. DVDMS-SDT will be advantageous for the management of small cell lung cancer due to its noninvasive characteristics.

scholarly journals Radiosynthesis, Biological Evaluation, and Preclinical Study of a 68Ga-Labeled Cyclic RGD Peptide as an Early Diagnostic Agent for Overexpressed αvβ3 Integrin Receptors in Non-Small-Cell Lung Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Nazanin Pirooznia ◽  
Khosrou Abdi ◽  
Davood Beiki ◽  
Farshad Emami ◽  
Seyed Shahriar Arab ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Specific Binding ◽  
Small Cell ◽  
Integrin Receptors ◽  
Small Cell Lung ◽  
Early Diagnostic

The αvβ3 integrin receptors have high expression on proliferating growing tumor cells of different origins including non-small-cell lung cancer. RGD-containing peptides target the extracellular domain of integrin receptors. This specific targeting makes these short sequences a suitable nominee for theranostic application. DOTA-E(cRGDfK)2 was radiolabeled with 68Ga efficiently. The in vivo and in vitro stability was examined in different buffer systems. Metabolic stability was assessed in mice urine. In vitro specific binding, cellular uptake, and internalization were determined. The tumor-targeting potential of [68Ga]Ga-DOTA-E(cRGDfK)2 in a lung cancer mouse model was studied. Besides, the very early diagnostic potential of the 68Ga-labeled RGD peptide was evaluated. The acquisition and reconstruction of the PET-CT image data were also carried out. Radiochemical and radionuclide purity for [68Ga]Ga-DOTA-E(cRGDfK)2 was >%98 and >%99, respectively. Radiotracer showed high in vivo, in vitro, and metabolic stability which was determined by ITLC. The dissociation constant (Kd) of [68Ga]Ga-DOTA-E(cRGDfK)2 was 15.28 nM. On average, more than 95% of the radioactivity was specific binding (internalized + surface-bound) to A549 cells. Biodistribution data showed that radiolabeled peptides were accumulated significantly in A549 tumor and excreted rapidly by the renal system. Tumor uptake peaks were at 1-hour postinjection for [68Ga]Ga-DOTA-E(cRGDfK)2. The tumor was clearly visualized in all images. [68Ga]Ga-DOTA-E(cRGDfK)2 can be used as a peptide-based imaging agent allowing very early detection of different cancers overexpressing αvβ3 integrin receptors and can be a potential candidate in clinical peptide-based imaging for lung cancer.

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