Synergistic Inhibition of Thalidomide and Icotinib on Human Non-Small Cell Lung Carcinomas Through ERK and AKT Signaling

Sun, Xiang; Yang, Xu; Wang, Yi; Chen, Qian; Liu, Liu; Bao, Yongzhan

doi:10.12659/msm.909977

Cited by 12 publications

(11 citation statements)

References 43 publications

(44 reference statements)

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“…In our analyses, low levels of MMP2 in imDCs corresponded to poor chemotactic migration. Curiously, however, we did not see activation of ERK heighten production of MMP2, as reported by others [ 44 ], so it is likely that the underlying mechanism is due to p38 [ 45 , 46 ] or other signaling pathways.…”

Section: Discussionsupporting

confidence: 73%

Effect of Selenium and Peroxynitrite on Immune Function of Immature Dendritic Cells in Humans

et al. 2021

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Background Selenium and peroxynitrite are known to support the growth and activity of immune cells, including T cells, B cells and macrophages. However, the role of these factors in the immune function of human immature dendritic cells (imDCs) is not clear. Material/Methods Monocytes from a mixture of blood samples were isolated using Ficoll density gradient centrifugation and purified with immunomagnetic beads before being induced into imDCs. Cells then either received no treatment (control group), or treatment with sodium selenite (Na 2 SeO 3 , Se), 3-morpholinosydnonimine (SIN1, which decomposes into peroxynitrite), or Se+SIN1. Cell viability, migration, and antiphagocytic abilities, oxidative stress, and protein expression of extracellular signal-regulated kinases (ERK) and MMP2 were assessed using a CCK8 assay, cell counter and flow cytometry, microplate spectrophotometer, and Western blot analysis, respectively. Results Viability of imDCs was unaffected by 0.1 μmol/L of Na 2 SeO 3 , although 1 mmol/L of SIN1 decreased it significantly ( P <0.05). Chemotactic migration and antiphagocytic abilities were inhibited and enhanced, respectively, by treatment with Na 2 SeO 3 and SIN1 ( P <0.05). Activities of superoxide dismutase and glutathione peroxidase were increased by Na 2 SeO 3 and Se+SIN1 ( P <0.001). Glutathione content decreased with exposure to Na 2 SeO 3 and SIN1 ( P <0.05), but increased after treatment with Se+SIN1 ( P <0.05). Levels of reactive oxygen species only increased with SIN1 treatment ( P <0.05). Treatment with Na 2 SeO 3 , SIN1 and Se+SIN1 increased ERK phosphorylation and decreased MMP2 protein expression ( P <0.05). Conclusions Selenium and peroxynitrite can influence immune function in imDCs by regulating levels of reactive oxygen species or glutathione to activate ERK and promote antigen phagocytosis, as well as by decreasing MMP2 expression to inhibit chemotactic migration.

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Section: Discussionsupporting

confidence: 73%

Effect of Selenium and Peroxynitrite on Immune Function of Immature Dendritic Cells in Humans

et al. 2021

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“…Until now, studies [20,21] have reported several EGFR gene mutations, such as exon 19 deletion, exon 21 L858R, exon 20 insertion, exon 21 L861Q, and exon 18G719X. However, EGFR gene mutations distribution in NSCLC patients with different ages or genders, has not been clarified.…”

Section: Discussionmentioning

confidence: 99%

Epidermal Growth Factor Receptor (EGFR) Mutations and Anaplastic Lymphoma Kinase/Oncogene or C-Ros Oncogene 1 (ALK/ROS1) Fusions Inflict Non-Small Cell Lung Cancer (NSCLC) Female Patients Older Than 60 Years of Age

Jiang

et al. 2018

Med Sci Monit

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BackgroundLung cancer has become a leading disease for the tumor-induced mortality. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancers. The present research aimed to evaluate the correlation between the anaplastic lymphoma kinase/oncogene or c-ros oncogene 1 (ALK/ROS1) fusions or mutations of epidermal growth factor receptor (EGFR) and ages or gender of patients.Material/MethodsAmong 1449 NSCLC patients, 457 patients who were diagnosed as consecutive EGFR mutations or ALK/ROS1 fusions between November 2016 and February 2018 were involved in the present study. EGFR genes or ALK/ROS1 mutations were detected by using DNA sequencing technique and amplification-refractory mutation system (ARMS). The mRNAs of ROS1 and ALK fusion were examined by using polymerase chain reaction technique and fusion gene detection kit.ResultsFemales were more often inflicted by the EGFR mutations, especially for the exon 19 deletion and L858R mutation. There were significantly more ALK/ROS1 fusions in females compared to males (P<0.05) and significantly more ALK/ROS1 fusions in <60 years of age patients compared to patients older than 60 years of age (P<0.05). Exon 21 L858R and L861Q dominantly occurred in patients ≥60 years of age and exon 19 deletion in patients <60 years of age. EML-ALK-1 mainly existed in the female NSCLC patients.ConclusionsEGFR mutations and ALK/ROS1 fusions mainly occurred in the NSCLC female patients who were older than 60 years of age.

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“…We selected A549, an adenocarcinomic human alveolar basal epithelial cell line to test our hypothesis that thalidomide would be effective against the cytokine storms. The A549 cell line is an appropriate model for testing cytokine storm targeting drugs since a previous study established this model by infecting the cells with influenza A/H1N1 virus (PR-8) or nonstructural protein 1 (NS1) plasmid to test the mechanisms behind inflammatory cytokines/chemokines mediated "cytokine storm" 34 Studies have utilized A549 cells to show the effects of thalidomide on lung fibrosis [35][36][37] . A limitation of this study is that only 978 genes called "landmark genes" are profiled in the iLINCS drug signatures.…”

Section: Discussionmentioning

confidence: 99%

Repurposing of thalidomide and its derivatives for the treatment of SARS-coV-2 infections: Hints on molecular action

Sundaresan

Giri

Singh

et al. 2020

Preprint

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Background and Purpose: SARS-coV-2 pandemic continues to cause an unprecedented global destabilization. There is an urgent need to develop vaccines or identify molecules to treat severe cases and repurposing of drugs is the best approach at this hour. Thalidomide, despite having an infamous history has been successfully repurposed and tested for various disease conditions including inflammatory diseases and tumor. Few reports emphasize the use of thalidomide with a SARS-coV-2 pneumonia patient being successfully treated with thalidomide. Experimental Approach: A meta-analysis comparing the transcriptomes of SARS-coV-2 infected tissues with thalidomide and lenalidomide-induced transcriptomic changes in transformed lung, endothelial and hematopoietic models was performed. Key Results: Thalidomide and lenalidomide exhibited pleiotropic effects affecting a range of biological processes including inflammation, immune response, angiogenesis, MAPK signaling, NOD-like receptor signaling, TLR signaling, leukocyte differentiation and innate immunity, the processes which are aberrantly regulated in severe COVID-19 patients. In addition, we show the similarities between the expression profiles of SARS-coV-2 infected lung and systemic lupus erythematous. Conclusion and Implications: The present study recommends thalidomide analogs as a "better fit" to treat severe cases of novel viral infections, healing the damaged network by compensating the impairment caused by the Coronavirus disease-2019 (COVID-19).

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Synergistic Inhibition of Thalidomide and Icotinib on Human Non-Small Cell Lung Carcinomas Through ERK and AKT Signaling

Cited by 12 publications

References 43 publications

Effect of Selenium and Peroxynitrite on Immune Function of Immature Dendritic Cells in Humans

Effect of Selenium and Peroxynitrite on Immune Function of Immature Dendritic Cells in Humans

Epidermal Growth Factor Receptor (EGFR) Mutations and Anaplastic Lymphoma Kinase/Oncogene or C-Ros Oncogene 1 (ALK/ROS1) Fusions Inflict Non-Small Cell Lung Cancer (NSCLC) Female Patients Older Than 60 Years of Age

Repurposing of thalidomide and its derivatives for the treatment of SARS-coV-2 infections: Hints on molecular action

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