Dexamethasone and lenvatinib inhibit migration and invasion of non‑small cell lung cancer by regulating EKR/AKT and VEGF signal pathways

Zhang, Daye; Zhang, Yongxiang; Cai, Zeyuan; Tu, Ying; Hu, Zhan-Song

doi:10.3892/etm.2019.8225

Cited by 11 publications

(11 citation statements)

References 42 publications

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“…Dexamethasone was shown to interfere with NF-κB activation and reduced TNF-α production [ 87 , 88 ]. In NSCLC cells it was shown to inhibit TGF-β1-induced migration as well as EMT via the AKT/ERK signaling pathways [ 89 ], suggesting a modulatory effect on CSC properties. Nevertheless, dexamethasone is also suggested to impair chemotherapy efficacy, as co-administration was shown to decrease chemosensitivity in NSCLC xenograft models [ 90 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Primary Human Cancer Stem-Like Cell Populations from Non-Small Cell Lung Cancer: Inhibition of Cell Survival by Targeting NF-κB and MYC Signaling

Windmöller

Beshay²,

Helweg

et al. 2021

Cells

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There is growing evidence that cancer stem cells (CSCs), a small subpopulation of self-renewal cancer cells, are responsible for tumor growth, treatment resistance, and cancer relapse and are thus of enormous clinical interest. Here, we aimed to isolate new CSC-like cells derived from human primary non-small cell lung cancer (NSCLC) specimens and to analyze the influence of different inhibitors of NF-κB and MYC signaling on cell survival. CSC-like cells were established from three squamous cell carcinomas (SCC) and three adenocarcinomas (AC) of the lung and were shown to express common CSC markers such as Prominin-1, CD44-antigen, and Nestin. Further, cells gave rise to spherical cancer organoids. Inhibition of MYC and NF-κB signaling using KJ-Pyr-9, dexamethasone, and pyrrolidinedithiocarbamate resulted in significant reductions in cell survival for SCC- and AC-derived cells. However, inhibition of the protein–protein interaction of MYC/NMYC proto-oncogenes with Myc-associated factor X (MAX) using KJ-Pyr-9 revealed the most promising survival-decreasing effects. Next to the establishment of six novel in vitro models for studying NSCLC-derived CSC-like populations, the presented investigations might provide new insights into potential novel therapies targeting NF-κB/MYC to improve clinical outcomes in NSCLC patients. Nevertheless, the full picture of downstream signaling still remains elusive.

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Section: Discussionmentioning

confidence: 99%

Novel Primary Human Cancer Stem-Like Cell Populations from Non-Small Cell Lung Cancer: Inhibition of Cell Survival by Targeting NF-κB and MYC Signaling

Windmöller

Beshay²,

Helweg

et al. 2021

Cells

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“…VEGF and the MMP family were reported to be closely related to lung cancer malignancy and even metastasis ( Merchant et al, 2017 ; Zhang et al, 2020a ). To determine the mechanisms for why ropivacaine inhibited the invasion and metastasis of lung cancer cells, we detected by western blot the VEGF and MMP protein expression levels in H1299 and A549 cells after ropivacaine treatment.…”

Section: Resultsmentioning

confidence: 99%

Ropivacaine Inhibits Lung Cancer Cell Malignancy Through Downregulation of Cellular Signaling Including HIF-1α In Vitro

et al. 2022

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Background: Ropivacaine is widely used to induce regional anesthesia during lung cancer surgery. Previous studies reported that amide-linked local anesthetics, e.g., ropivacaine, affected the biological behavior of lung adenocarcinoma cells, but the conclusion is controversial and warrants further study. This study set out to investigate the biological effects of ropivacaine on cultured lung cancer cells and underlying mechanisms.Methods: Lung cancer cell lines (A549 and H1299) were cultured and then treated with or without ropivacaine (0.5, 1, and 2 mM) for 48 or 72 h. Their proliferation, migration, and invasion together with cell death and molecules including hypoxia inducible factor (HIF)-1α, VEGF, matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9 expression associated with these changes were determined.Results: Ropivacaine significantly inhibited proliferation and migration, invasion, and cell death in a concentration-dependent manner in both cell lines. Ropivacaine also promoted cell death and induced a concentration- and time-dependent cell arrest towards the G0/G1 phase. Expression of VEGF, MMP-1, MMP-2, MMP-9, and HIF-1α in both cell lines was also inhibited by ropivacaine in a concentration-related manner.Conclusion: Our data indicated that ropivacaine inhibited lung cancer cell malignancy, which may be associated with downregulation of cell-survival-associated cellular molecules. The translational value of the current work is subjected to further study.

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“…Li-Qing Du and colleague noticed that this drug inhibit the expression of RAD51 in cancer cells 48 . Daye Zhang et al reported that Lenvatinib and Dexamethasone inhibit the invasion and migration of NSCLC 49 . According to Haiyan Ge and colleagues, pemetrexed-induced senescence alleviates in NSCLC by Dexamethasone 50 .…”

Section: Resultsmentioning

confidence: 99%

Drug repositioning in non-small cell lung cancer (NSCLC) using gene co-expression and drug–gene interaction networks analysis

MotieGhader

Tabrizi-Nezhadi

Paskeh

et al. 2022

Sci Rep

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Lung cancer is the most common cancer in men and women. This cancer is divided into two main types, namely non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Around 85 to 90 percent of lung cancers are NSCLC. Repositioning potent candidate drugs in NSCLC treatment is one of the important topics in cancer studies. Drug repositioning (DR) or drug repurposing is a method for identifying new therapeutic uses of existing drugs. The current study applies a computational drug repositioning method to identify candidate drugs to treat NSCLC patients. To this end, at first, the transcriptomics profile of NSCLC and healthy (control) samples was obtained from the GEO database with the accession number GSE21933. Then, the gene co-expression network was reconstructed for NSCLC samples using the WGCNA, and two significant purple and magenta gene modules were extracted. Next, a list of transcription factor genes that regulate purple and magenta modules' genes was extracted from the TRRUST V2.0 online database, and the TF–TG (transcription factors–target genes) network was drawn. Afterward, a list of drugs targeting TF–TG genes was obtained from the DGIdb V4.0 database, and two drug–gene interaction networks, including drug-TG and drug-TF, were drawn. After analyzing gene co-expression TF–TG, and drug–gene interaction networks, 16 drugs were selected as potent candidates for NSCLC treatment. Out of 16 selected drugs, nine drugs, namely Methotrexate, Olanzapine, Haloperidol, Fluorouracil, Nifedipine, Paclitaxel, Verapamil, Dexamethasone, and Docetaxel, were chosen from the drug-TG sub-network. In addition, nine drugs, including Cisplatin, Daunorubicin, Dexamethasone, Methotrexate, Hydrocortisone, Doxorubicin, Azacitidine, Vorinostat, and Doxorubicin Hydrochloride, were selected from the drug-TF sub-network. Methotrexate and Dexamethasone are common in drug-TG and drug-TF sub-networks. In conclusion, this study proposed 16 drugs as potent candidates for NSCLC treatment through analyzing gene co-expression, TF–TG, and drug–gene interaction networks.

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Dexamethasone and lenvatinib inhibit migration and invasion of non‑small cell lung cancer by regulating EKR/AKT and VEGF signal pathways

Cited by 11 publications

References 42 publications

Novel Primary Human Cancer Stem-Like Cell Populations from Non-Small Cell Lung Cancer: Inhibition of Cell Survival by Targeting NF-κB and MYC Signaling

Novel Primary Human Cancer Stem-Like Cell Populations from Non-Small Cell Lung Cancer: Inhibition of Cell Survival by Targeting NF-κB and MYC Signaling

Ropivacaine Inhibits Lung Cancer Cell Malignancy Through Downregulation of Cellular Signaling Including HIF-1α In Vitro

Drug repositioning in non-small cell lung cancer (NSCLC) using gene co-expression and drug–gene interaction networks analysis

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