scholarly journals Dendrobine Inhibits γ-Irradiation-Induced Cancer Cell Migration, Invasion and Metastasis in Non-Small Cell Lung Cancer Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 954
Author(s):  
Ye-Ram Kim ◽  
Ah-Reum Han ◽  
Jin-Baek Kim ◽  
Chan-Hun Jung
Keyword(s):  
Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Migration And Invasion ◽  
Inhibitory Effects ◽  
Invasion And Metastasis ◽  
Small Cell Lung ◽  
Γ Irradiation

The use of ionizing radiation (IR) during radiotherapy can induce malignant effects, such as metastasis, which contribute to poor prognoses in lung cancer patients. Here, we explored the ability of dendrobine, a plant-derived alkaloid from Dendrobium nobile, to improve the efficacy of radiotherapy in non-small cell lung cancer (NSCLC). We employed Western blotting, quantitative real-time (qRT)-PCR, transwell migration assays, and wound-healing assays to determine the effects of dendrobine on the migration and invasion of A549 lung cancer cells in vitro. Dendrobine (5 mm) inhibited γ-irradiation-induced migration and invasion of A549 cells by suppressing sulfatase2 (SULF2) expression, thus inhibiting IR-induced signaling. To investigate the inhibitory effects of dendrobine in vivo, we established a mouse model of IR-induced metastasis by injecting BALB/c nude mice with γ-irradiated A549 cells via the tail vein. As expected, injection with γ-irradiated cells increased the number of pulmonary metastatic nodules in mice (0 Gy/DPBS, 9.8 ± 1.77; 2 Gy/DPBS, 20.87 ± 1.42), which was significantly reduced with dendrobine treatment (2 Gy/Dendrobine, 10.87 ± 0.71), by prevention of IR-induced signaling. Together, these findings demonstrate that dendrobine exerts inhibitory effects against γ-irradiation-induced invasion and metastasis in NSCLC cells in vitro and in vivo at non cytotoxic concentrations. Thus, dendrobine could serve as a therapeutic enhancer to overcome the malignant effects of radiation therapy in patients with NSCLC.

scholarly journals SNP rs4142441 and MYC co-modulated long non-coding RNA OSER1-AS1 suppresses non-small cell lung cancer by sequestering RNA-Binding Protein ELAVL1

2020 ◽  
Author(s):  
Weijia Xie ◽  
Youhao Wang ◽  
Yao Zhang ◽  
Ying Xiang ◽  
Na Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Rna Binding ◽  
Lung Cancer Risk ◽  
Rna Binding Protein ◽  
Small Cell ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Small Cell Lung

Abstract Background: Single nucleotide polymorphisms (SNPs) and long non-coding RNAs (lncRNAs) have been involved in the process of lung cancer. Following clues given by lung cancer risk-associated SNPs, we aimed to find novel functional lncRNAs as candidate targets in non-small cell lung cancer (NSCLC). Methods: Case-control analyses were performed in 626 cases and 736 controls matched up on sex and age. The lncRNA OSER1-AS1 was identified near a lung cancer risk-associated SNP rs4142441. Kaplan–Meier survival analysis was performed to investigate the association between OSER1-AS1 expression and overall survival. The influence of rs4142441 on the expression level of OSER1-AS1 was confirmed using Luciferase assays. Subsequently, the biological function of OSER1-AS1 was assessed in vitro by cell proliferation, migration, and invasion experiments through gain- and loss-of-function approaches, and in vivo by subcutaneous tumor model and tail vein injection lung metastasis model. ChIP and RIP experiments were carried out to investigate the interaction between transcription factors, RNA-binding proteins, and OSER1-AS1.Results: OSER1-AS1 was down-regulated in tumor tissue and its low expression was significantly associated with poor overall survival among non-smokers in NSCLC patients. Gain- and loss-of-function studies revealed that OSER1-AS1 acted as a tumor suppressor by inhibiting lung cancer cell growth, migration and invasion in vitro. Xenograft tumor assays and metastasis mouse model confirmed that OSER1-AS1 suppressed tumor growth and metastasis in vivo. The promoter of OSER1-AS1 was repressed by MYC, and the 3’-end of OSER1-AS1 was competitively targeted by microRNA hsa-miR-17-5p and RNA-binding protein ELAVL1. Conclusion: Our results indicated that OSER1-AS1 exerted tumor-suppressive functions by acting as an ELAVL1 decoy to keep it away from its target mRNAs. Our findings characterized OSER1-AS1 as a new tumor suppressive lncRNA in NSCLC, suggesting that OSER1-AS1 may be suitable as a potential biomarker for prognosis, and a potential target for treatment.

scholarly journals PPy@Fe3O4 Nanoparticles Inhibit Tumor Growth and Metastasis Through Chemodynamic and Photothermal Therapy in Non-small Cell Lung Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Danruo Fang ◽  
Hansong Jin ◽  
Xiulin Huang ◽  
Yongxin Shi ◽  
Zeyu Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Photothermal Therapy ◽  
Synergistic Effects ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung

Non-small cell lung cancer (NSCLC) is considered to be a principal cause of cancer death across the world, and nanomedicine has provided promising alternatives for the treatment of NSCLC in recent years. Photothermal therapy (PTT) and chemodynamic therapy (CDT) have represented novel therapeutic modalities for cancer treatment with excellent performance. The purpose of this research was to evaluate the effects of PPy@Fe3O4 nanoparticles (NPs) on inhibiting growth and metastasis of NSCLC by combination of PTT and CDT. In this study, we synthesized PPy@Fe3O4 NPs through a very facile electrostatic absorption method. And we detected reactive oxygen species production, cell apoptosis, migration and protein expression in different groups of A549 cells and established xenograft models to evaluate the effects of PPy@Fe3O4 NPs for inhibiting the growth of NSCLC. The results showed that the PPy@Fe3O4 NPs had negligible cytotoxicity and could efficiently inhibit the cell growth and metastasis of NSCLC in vitro. In addition, the PPy@Fe3O4 NPs decreased tumor volume and growth in vivo and endowed their excellent MRI capability of observing the location and size of tumor. To sum up, our study displayed that the PPy@Fe3O4 NPs had significant synergistic effects of PTT and CDT, and had good biocompatibility and safety in vivo and in vitro. The PPy@Fe3O4 NPs may be an effective drug platform for the treatment of NSCLC.

scholarly journals Antitumor Activity of DFX117 by Dual Inhibition of c-Met and PI3Kα in Non-Small Cell Lung Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 627 ◽  
Author(s):  
Yanhua Fan ◽  
Huaiwei Ding ◽  
Donghwa Kim ◽  
Duc-Hiep Bach ◽  
Ji-Young Hong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Antitumor Activity ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Pik3ca Mutation ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung

Aberrant activation of hepatocyte growth factor (HGF)/c-Met signaling pathway caused by gene amplification or mutation plays an important role in tumorigenesis. Therefore, c-Met is considered as an attractive target for cancer therapy and c-Met inhibitors have been developed with great interests. However, cancers treated with c-Met inhibitors inevitably develop resistance commonly caused by the activation of PI3K/Akt signal transduction pathway. Therefore, the combination of c-Met and PI3Kα inhibitors showed synergistic activities, especially, in c-Met hyperactivated and PIK3CA-mutated cells. In our previous study, we rationally designed and synthesized DFX117(6-(5-(2,4-difluorophenylsulfonamido)-6-methoxypyridin-3-yl)-N-(2-morpholinoethyl) imidazo[1,2-a]pyridine-3-carboxamide) as a novel PI3Kα selective inhibitor. Herein, the antitumor activity and underlying mechanisms of DFX117 against non-small cell lung cancer (NSCLC) cells were evaluated in both in vitro and in vivo animal models. Concurrent targeted c-Met and PI3Kα by DFX117 dose-dependent inhibited the cell growth of H1975 cells (PIK3CA mutation and c-Met amplification) and A549 cells (KRAS mutation). DFX117 subsequently induced G0/G1 cell cycle arrest and apoptosis. These data highlight the significant potential of DFX117 as a feasible and efficacious agent for the treatment of NSCLC patients.

scholarly journals Engineered exosomes loaded with miR-449a selectively inhibit the growth of homologous non-small cell lung cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wen Zhou ◽  
Mingming Xu ◽  
Zhipeng Wang ◽  
Mingjun Yang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Transfection Efficiency ◽  
Drug Carrier ◽  
A549 Cells ◽  
Small Cell ◽  
Small Cell Lung

AbstractAs an efficient drug carrier, exosome has been widely used in the delivery of genetic drugs, chemotherapeutic drugs, and anti-inflammatory drugs. As a genetic drug carrier, exosomes are beneficial to improve transfection efficiency and weaken side effects at the same time. Here, we use genetic engineering to prepare engineered exosomes (miR-449a Exo) that can actively deliver miR-449a. It was verified that miR-449a Exo had good homology targeting capacity and was specifically taken up by A549 cells. Moreover, miR-449a Exo had high delivery efficiency of miR-449a in vitro and in vivo. We demonstrated that miR-449a Exo effectively inhibited the proliferation of A549 cells and promoted their apoptosis. In addition, miR-449a Exo was found to control the progression of mouse tumors and prolong their survival in vivo. Our research provides new ideas for exosomes to efficiently and actively load gene drugs, and finds promising methods for the treatment of non-small cell lung cancer.

scholarly journals High-intensity focused ultrasound enhances the cisplatin sensitivity to human non-small cell lung cancer in vitro and in vivo

2021 ◽  
Author(s):  
Liwei Wang ◽  
Huijun Fan ◽  
Haiyan Wang ◽  
Yunlu Bai ◽  
Wenyan Zhou
Keyword(s):  
Focused Ultrasound ◽  
Nsclc Patient ◽  
A549 Cells ◽  
Xenograft Model ◽  
Small Cell ◽  
High Intensity Focused Ultrasound ◽  
Migration And Invasion ◽  
Small Cell Lung

Abstract BackgroundThe incidence and mortality of non-small cell lung cancer (NSCLC) rank first among malignant tumors worldwide. Cisplatin (CDDP) is currently the first-line chemotherapy drug used in clinical practice. However, the underlying mechanism that NSCLC cells are resistant to CDDP has not been fully elucidated. Therefore, it is urgent to explore the exact function of chemotherapy resistance and improve the anti-tumor effect of CDDP treatment.MethodWe investigated the surviving fraction of H1299 and A549 cells treated with different High-intensity focused ultrasound (HIFU) and various CDDP concentrations. HIFU (400W/cm2) and CDDP (10 μM) were selected to probe the further function in H1299 and A549 cells. Flow cytometry, MTT, and colony formation assays were performed to evaluate the apoptosis and proliferative effect of HIFU and CDDP on NSCLC cells. Transwell assays were used to analyze the migration and invasion abilities of NSCLC cells with HIFU and CDDP treatments. Platinum (Pt) accumulation was further measured in H1299 and A549 cells with different treatments. Finally, An NSCLC patient-derived xenograft model was used to explore the effect of HIFU and CDDP on NSCLC tumor growth.ResultsHIFU combined with CDDP can markedly reduce the surviving rate and promote the apoptosis of NSCLC cells. Furthermore, co-treatment with HIFU and CDDP significantly inhibited the proliferation, colony formation, migration, and invasion of NSCLC cells compared to that with any single treatment. Moreover, the combined therapy can effectively promote Pt accumulation in NSCLC cells. Further functional analysis suggested that HIFU combined with CDDP can inhibit tumor growth in an NSCLC patient-derived xenograft model. Finally, the CDDP method effectively upregulated the expression level of apoptosis-related protein, cleaved-PARP, which could be further enhanced by the HIFU treatment.ConclusionOur results revealed that HIFU enhances the anti-NSCLC effect of CDDP both in vitro and in vivo, providing a promising combination therapy for clinical NSCLC treatment.

scholarly journals MiR-224 Promotes Lymphatic Metastasis by Targeting ANGPTL1 in Non-Small-Cell Lung Carcinoma

2021 ◽  
Author(s):  
Haibo Han ◽  
Bo Pan ◽  
Fan Liang ◽  
Lina Wu ◽  
Xijuan Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lymphatic Metastasis ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Potential Marker

Abstract Background: MicroRNAs can regulates tumor metastasis either as an oncomiR or suppressor miRNA. Here, we investigate the role of miR-224 in lymphatic metastasis of non-small-cell lung cancer (NSCLC). Methods: The expression of miR-224 was demonstrated by a validation cohort of 156 lung cancer patients (77 cases with lymphatic metastasis) by q-PCR. In vitro and in vivo experiments were performed to study the malignant phenotype after upregulation and inhibition of miR-224 expression. Furthermore, the direct target genes of miR-224 were determined by a luciferase reporter assay. Results: miR-224 was identified as a high expression miRNA in the tumor tissues with lymphatic metastasis) with an area under the receiver operating characteristic curve (AUC) of 0.57. Forced expression of miR-224 in H1299 cells promoted not only the cell viability, plate clone formation, migration and invasion in vitro, but also tumor growth and lung metastasis in vivo. Consistently, inhibition of miR-224 suppressed the malignant characters both in vitro and in vivo. Molecular mechanism research suggested that miR-422a targeted the ANGPTL1 as a novel tumor suppressor.Conclusions: The present study demonstrates that miR-224 is a potential marker for the prediction of lymphatic metastasis of NSCLC. And application of miR-224 may help for prophylactic intervention of NSCLC in clinical practice.

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