scholarly journals FNC Inhibits Proliferation and Metastasis of Non-Small-Cell Lung Cancer in Vivo and In Vitro

2021 ◽  
Author(s):  
Xiang Jing ◽  
Shuai Niu ◽  
Yi Liang ◽  
Huiping Chen ◽  
Ning Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Dependent Manner ◽  
Small Cell Lung ◽  
H460 Cells ◽  
Proliferation And Metastasis

Abstract Background: Non-small-cell lung cancer (NSCLC) is associated with the highest morbidity and mortality rate, and chemotherapy is the primary therapy for NSCLC. However, the clinical outcome is still far from satisfactory. This study aimed to determine the effects and mechanisms of FNC on NSCLC. Results: FNC, 2'-deoxy-2'-β-fluoro-4'-azidocytidine, is a novel cytidine analogue, inhibits the proliferation and metastasis of H460 cells in a time- and dose-dependent manner in vitro. Mechanistically, treatment of H460 cells with FNC inhibits Bcl-2 expression and potentiates Cytochrome C (Cyt-C) release, Bax and caspase-3 expression. In parallel, FNC inhibits tumor migration, invasion and metastasis in H460 cells by increasing E-cadherin protein levels and reducing the expression of VEGF, MMP-2, MMP-9 proteins. And murine models and mouse xenograft models also proved that FNC could significantly inhibit NSCLC tumor growth and metastasis with low toxicity. Finally, we also discovered that inhibition of DNMT3B expression is one of the important mechanisms of FNC inhibiting proliferation and metastasis of NSCLC cells. Conclusions: FNC induces apoptosis through the mitochondrial apoptotic pathway and represses tumor progression by targeting multiple proteins related to cell adhesion and invasion in vitro and in vivo. Meanwhile, FNC was involved in regulating DNA methylation. In summary, our results support the further development of FNC as potential therapeutics for clinical non-small cell lung cancer.

SIRT2 suppresses non-small cell lung cancer growth by targeting JMJD2A

2015 ◽  
Vol 396 (8) ◽  
pp. 929-936 ◽  
Author(s):  
Weihua Xu ◽  
Kanqiu Jiang ◽  
Mingjing Shen ◽  
Yongyue Qian ◽  
Yong Peng
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Disease Free Survival ◽  
Small Cell ◽  
Cancer Growth ◽  
Dependent Manner ◽  
Small Cell Lung

Abstract Lung cancer has been the most prolific cancer in China – as in the rest of the world – with a high death rate and low 5-year survival rate. Previous evidence showed that JMJD2A is over-expressed in human non-small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues, and that high level of JMJD2A predicts poor overall and disease-free survival. However, the mechanism by which JMJD2A is regulated in human NSCLC is not fully understood. In the present study, we identified that the SIRT2 as an anti-oncogenic protein in NSCLC was down-regulated. JMJD2A as a target of SIRT2 was negatively correlated with SIRT2 level in NSCLC. SIRT2 bound to the promoter region of JMJD2A and negatively regulated JMJD2A expression. In addition, we found that SIRT2 inhibited NSCLC cells proliferation, colony formation and tumor growth in vitro and in vivo in a JMJD2A-dependent manner. In summary, our findings implicate that SIRT2 suppresses non-small cell lung cancer growth through targeting JMJD2A and SIRT2 activator may serve as candidate drug for NSCLC therapy.

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 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.

scholarly journals Micheliolide Enhances Radiosensitivities of p53-Deficient Non-Small-Cell Lung Cancer via Promoting HIF-1α Degradation

2020 ◽  
Vol 21 (9) ◽  
pp. 3392
Author(s):  
Peizhong Kong ◽  
K.N. Yu ◽  
Miaomiao Yang ◽  
Waleed Abdelbagi Almahi ◽  
Lili Nie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Hypoxic Exposure ◽  
Dependent Manner ◽  
Wild Type ◽  
Small Cell Lung ◽  
H460 Cells ◽  
Wild Type P53

Micheliolide (MCL) has shown promising anti-inflammatory and anti-tumor efficacy. However, whether and how MCL enhances the sensitivity of non-small-cell lung cancer (NSCLC) to radiotherapy are still unknown. In the present paper, we found that MCL exerted a tumor cell killing effect on NSCLC cells in a dose-dependent manner, and MCL strongly sensitized p53-deficient NSCLC cells, but not the cells with wild-type p53 to irradiation (IR). Meanwhile, MCL markedly inhibited the expression of hypoxia-inducible factor-1α (HIF-1α) after IR and hypoxic exposure in H1299 and Calu-1 cells rather than in H460 cells. Consistently, radiation- or hypoxia-induced expression of vascular endothelial growth factor (VEGF) was also significantly inhibited by MCL in H1299 and Calu-1 cells, but not in H460 cells. Therefore, inhibition of the HIF-1α pathway might, at least in part, contribute to the radiosensitizing effect of MCL. Further study showed that MCL could accelerate the degradation of HIF-1α through the ubiquitin-proteosome system. In addition, the transfection of wild-type p53 into p53-null cells (H1299) attenuated the effect of MCL on inhibiting HIF-1α expression. These results suggest MCL effectively sensitizes p53-deficient NSCLC cells to IR in a manner of inhibiting the HIF-1α pathway via promoting HIF-1α degradation, and p53 played a negative role in MCL-induced HIF-1α degradation.

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