Transcription Factor p53 Suppresses Tumor Growth by Prompting Pyroptosis in Non-Small-Cell Lung Cancer

Objective. To evaluate the effect of p53 on pyroptosis and its inhibitory role on tumor growth in non-small-cell lung cancer (NSCLC). Methods. The correlation of p53 and pyroptosis was determined in tumor tissues of NSCLC patients. The pyroptotic level was detected in A549 cells to clarify the effect of p53 on pyroptosis. p53 overexpression A549 tumor-bearing mice were used to clarify the therapeutic target of p53 in NSCLC treatment. Results. p53 expression level was positively related to pyroptosis in NSCLC tissues. In in vitro assays, p53 directly regulated pyroptosis in A549 cells. p53-specific knockdown blocked lipopolysaccharide- (LPS-) induced pyroptosis. In in vivo assays, p53 overexpression in A549 markedly decreased tumor growth and death rate by increasing the pyroptotic level. Conclusions. Upregulation of p53 prompts pyroptosis to produce anti-NSCLC effects suggesting the potential of p53 on suppressing tumor growth in NSCLC patients.

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Up-regulated HMGB1 in the pleural effusion of non-small cell lung cancer (NSCLC) patients reduces the chemosensitivity of NSCLC cells

Tumori Journal ◽

10.5301/tj.5000656 ◽

2018 ◽

Vol 104 (5) ◽

pp. 338-343 ◽

Cited By ~ 6

Author(s):

Ying Ma ◽

Shirong Kang ◽

Xu Wu ◽

Bateer Han ◽

Zhiyong Jin ◽

...

Keyword(s):

Lung Cancer ◽

Pleural Effusion ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

A549 Cells ◽

Small Cell ◽

Small Cell Lung ◽

Nsclc Patients

Background: Pleural effusion is one of the complications of human non-small cell lung cancer (NSCLC). High mobility group box-1 protein (HMGB1) correlates highly with invasion and metastasis in multiple tumors. The aim of this study was to explore the clinical value of HMGB1 in NSCLC patients, and to investigate the role of HMGB1 in the development of pleural effusion. In addition, we also investigated the regulatory role of HMGB1 in the sensitivity of NSCLC cells to cisplatin. Methods: 46 NSCLC malignant pleural effusion (MPE) and 31 benign pleural effusion samples were quantitatively analyzed with Enzyme-Linked Immunosorbent Assay (ELISA) for cytokines, such as IL-1beta, IL-6, IL-8 and HMGB1. The HMGB1 expression in NSCLC tissues was examined with RT-qPCR and western blotting methods. Then the influence by HMGB1 on the chemosensitivity of lung cancer A549 cells was examined with MTT assay and colony forming assay for the A549 cells post the treatment with cisplatin or (and) HMGB1. Results: The results demonstrated that HMGB1 was up-regulated in the pleural effusion of NSCLC patients, along with the up-regulated levels of proinflammatory cytokines such as IL-6 and IL-8. And the up-regulation of HMGB1 was confirmed at both the mRNA and protein levels in the NSCLC tissues. Recombinant HMGB1 reduced the sensitivity of A549 cells to cisplatin in vitro. Conclusions: In conclusion, HMGB1 was up-regulated in the pleural effusion and tumor tissues of NSCLC patients. HMGB1 reduced the sensitivity of NSCLC A549 cells to cisplatin in vitro.

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Regulatory Effects of Siegesbeckia glabrescens on Non-Small Cell Lung Cancer Cell Proliferation and Invasion

The American Journal of Chinese Medicine ◽

10.1142/s0192415x1450030x ◽

2014 ◽

Vol 42 (02) ◽

pp. 453-463 ◽

Cited By ~ 18

Author(s):

Ha Neul Lee ◽

Ji-Hye Joo ◽

Joa Sub Oh ◽

Shin Wook Choi ◽

Dong-Wan Seo

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

A549 Cells ◽

Ethanol Extract ◽

Small Cell ◽

Small Cell Lung ◽

P53 Expression ◽

Proliferation And Invasion

Siegesbeckia glabrescens (SG) Makino (Compositae) has been used as a traditional medicine for the treatment of allergic and inflammatory diseases. In the present study, we examined the effects and molecular mechanism of the ethanol extract of SG on cell proliferation and invasion in p53 wild-type A549 and p53-deficient H1299 non-small cell lung cancer (NSCLC) cells. SG treatment markedly inhibited the proliferation and invasion in both cell lines, independently of p53 expression. The anti-proliferative effect of SG on A549 cells was mediated by the inactivation of Akt and p70S6K as evidenced by treatment with LY294002 and rapamycin, respectively. In addition, anti-invasive activity of SG in A549 cells was found to be associated with the inhibition of p70S6K. In contrast, in H1299 cells the inactivation of p38MAPK appeared to be involved in SG-mediated inhibition of cell proliferation and invasion. Collectively, these findings suggest that SG modulates cellular fates such as proliferation and invasion by differential regulation of signaling pathways, depending on the status of p53 expression in NSCLC, and support the development of SG as a potent therapeutic agent for the treatment of NSCLC.

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MiR-424 Promotes Non-Small Cell Lung Cancer Progression and Metastasis through Regulating the Tumor Suppressor Gene TNFAIP1

Cellular Physiology and Biochemistry ◽

10.1159/000477314 ◽

2017 ◽

Vol 42 (1) ◽

pp. 211-221 ◽

Cited By ~ 19

Author(s):

Ming Zhang ◽

Chang’e Gao ◽

Yi Yang ◽

Gaofeng Li ◽

Jian Dong ◽

...

Keyword(s):

Lung Cancer ◽

Cell Migration ◽

Tumor Growth ◽

Small Cell Lung Cancer ◽

Cancer Progression ◽

Cell Lung Cancer ◽

A549 Cells ◽

Small Cell ◽

Luciferase Assay ◽

Small Cell Lung

Background/Aims: This study aimed to investigate the potential roles of miR-424 expression in non-small cell lung cancer (NSCLC) metastasis and growth and its underlying mechanism. Methods: The expression of miR-424 in two NSCLC cell lines (A549 and H1975) was altered by transfection with miR-424 mimic and inhibitor. Effects of miR-424 overexpression and suppression on cells migration, invasion and colony formation were analyzed. Target genes for miR-424 were predicted using bioinformatics method and then verified using luciferase assay. Effects of miR-424 expression on cell migration, invasion and proliferation were reanalyzed on the condition of TNFAIP1 was silenced. Moreover, TNFAIP1 silencing and miR-424 modified A549 cells were subcutaneous injected into node BALB/c mice to confirm the regulation of miR-424 on TNFAIP1 in regulating tumor growth. Results: Compared with the control, miR-424 overexpression significantly increased the migrated and invaded cells, as well as the proliferated colonies. TNFAIP1 was a predicted target gene for miR-424, and was negatively regulated by miR-424. TNFAIP1 silence significantly increased the migrated and invaded cells compared to that in control, while these increases were abolished by miR-424 suppression. Animal experiment further evidenced miR-424 affected tumor growth by regulating TNFAIP1. Conclusions: These data demonstrate that miR-424 may be a contributor for NSCLC progression and metastasis through involving in cell migration, invasion and proliferation via inhibiting TNFAIP1. This study may provide theoretical basis for miR-424 in NSCLC target therapeutic treatment.

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Multicenter Observational Study of Chinese Non-Small Cell Lung Cancer (NSCLC) Patients With Rare Driver Gene Mutation

Case Medical Research ◽

10.31525/ct1-nct04137718 ◽

2019 ◽

Author(s):

Keyword(s):

Lung Cancer ◽

Observational Study ◽

Small Cell Lung Cancer ◽

Gene Mutation ◽

Cell Lung Cancer ◽

Small Cell ◽

Driver Gene ◽

Small Cell Lung ◽

Multicenter Observational Study ◽

Nsclc Patients

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Phanginin R Induces Cytoprotective Autophagy via JNK/c-Jun Signaling Pathway in Non-Small Cell Lung Cancer A549 Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200414095828 ◽

2020 ◽

Vol 20 (8) ◽

pp. 982-988 ◽

Cited By ~ 1

Author(s):

Le-Le Zhang ◽

Han Bao ◽

Yu-Lian Xu ◽

Xiao-Ming Jiang ◽

Wei Li ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Signaling Pathway ◽

Cell Lung Cancer ◽

Biological Activities ◽

A549 Cells ◽

Immunofluorescence Assay ◽

Small Cell ◽

Autophagic Flux ◽

Small Cell Lung

Background: Cassane-type diterpenoids are widely distributed in the medical plants of genus Caesalpinia. To date, plenty of cassane diterpenoids have been isolated from the genus Caesalpinia, and some of them were documented to exhibit multiple biological activities. However, the effects of these compounds on autophagy have never been reported. Objective: To investigate the effects and mechanisms of the cassane diterpenoids including Phanginin R (PR) on autophagy in Non-Small Cell Lung Cancer (NSCLC) A549 cells. Methods: Western blot analysis and immunofluorescence assay were performed to investigate the effects of the compounds on autophagic flux in A549 cells. The pathway inhibitor and siRNA interference were used to investigate the mechanism of PR. MTT assay was performed to detect cell viability. Results: PR treatment upregulated the expression of phosphatidylethanolamine-modified microtubule-associated protein Light-Chain 3 (LC3-II) in A549 cells. Immunofluorescence assay showed that PR treatment increased the production of red-fluorescent puncta in mRFP-GFP-LC3 plasmid-transfected cells, indicating PR promoted autophagic flux in A549 cells. PR treatment activated the c-Jun N-terminal Kinase (JNK) signaling pathway while it did not affect the classical Akt/mammalian Target of Rapamycin (mTOR) pathway. Pretreatment with the JNK inhibitor SP600125 or siRNA targeting JNK or c-Jun suppressed PR-induced autophagy. In addition, cotreatment with the autophagy inhibitor Chloroquine (CQ) or inhibition of the JNK/c-Jun signaling pathway increased PR-induced cytotoxicity. Conclusion: PR induced cytoprotective autophagy in NSCLC A549 cells via the JNK/c-Jun signaling pathway, and autophagy inhibition could further improve the anti-cancer potential of PR.

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A nomogram model to predict death rate among non-small cell lung cancer (NSCLC) patients with surgery in surveillance, epidemiology, and end results (SEER) database

BMC Cancer ◽

10.1186/s12885-020-07147-y ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Bo Jia ◽

Qiwen Zheng ◽

Jingjing Wang ◽

Hongyan Sun ◽

Jun Zhao ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Death Rate ◽

Small Cell ◽

Seer Database ◽

Small Cell Lung ◽

Nsclc Patients ◽

End Results

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The association between the GSTP1 A313G and GSTM1 null/present polymorphisms and the treatment response of the platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients: a meta-analysis

Tumor Biology ◽

10.1007/s13277-014-1866-4 ◽

2014 ◽

Vol 35 (7) ◽

pp. 6791-6799 ◽

Cited By ~ 14

Author(s):

Yanlong Yang ◽

Lei Xian

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Treatment Response ◽

Cell Lung Cancer ◽

Meta Analysis ◽

Small Cell ◽

Small Cell Lung ◽

Platinum Based Chemotherapy ◽

Nsclc Patients

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Biomarkers and Gene Signatures to Predict Durable Response to Pembrolizumab in Non-Small Cell Lung Cancer

Cancers ◽

10.3390/cancers13153828 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3828

Author(s):

Anello Marcello Poma ◽

Rossella Bruno ◽

Iacopo Pietrini ◽

Greta Alì ◽

Giulia Pasquini ◽

...

Keyword(s):

Lung Cancer ◽

T Cells ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Immune Cell ◽

Small Cell ◽

Small Cell Lung ◽

First Line ◽

Durable Response ◽

Nsclc Patients

Pembrolizumab has been approved as first-line treatment for advanced Non-small cell lung cancer (NSCLC) patients with tumors expressing PD-L1 and in the absence of other targetable alterations. However, not all patients that meet these criteria have a durable benefit. In this monocentric study, we aimed at refining the selection of patients based on the expression of immune genes. Forty-six consecutive advanced NSCLC patients treated with pembrolizumab in first-line setting were enrolled. The expression levels of 770 genes involved in the regulation of the immune system was analysed by the nanoString system. PD-L1 expression was evaluated by immunohistochemistry. Patients with durable clinical benefit had a greater infiltration of cytotoxic cells, exhausted CD8, B-cells, CD45, T-cells, CD8 T-cells and NK cells. Immune cell scores such as CD8 T-cell and NK cell were good predictors of durable response with an AUC of 0.82. Among the immune cell markers, XCL1/2 showed the better performance in predicting durable benefit to pembrolizumab, with an AUC of 0.85. Additionally, CD8A, CD8B and EOMES showed a high specificity (>0.86) in identifying patients with a good response to treatment. In the same series, PD-L1 expression levels had an AUC of 0.61. The characterization of tumor microenvironment, even with the use of single markers, can improve patients’ selection for pembrolizumab treatment.

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Circulating Biomarkers of Response and Toxicity of Immunotherapy in Advanced Non-Small Cell Lung Cancer (NSCLC): A Comprehensive Review

Cancers ◽

10.3390/cancers13081794 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1794

Author(s):

Alice Indini ◽

Erika Rijavec ◽

Francesco Grossi

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Liquid Biopsy ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitors ◽

Small Cell ◽

Circulating Biomarkers ◽

Small Cell Lung ◽

Nsclc Patients

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death (PD)-1 protein and its ligand, PD-L1, and cytotoxic T-lymphocyte-associated antigen (CTLA)-4, have revolutionized the management of patients with advanced non-small cell lung cancer (NSCLC). Unfortunately, only a small portion of NSCLC patients respond to these agents. Furthermore, although immunotherapy is usually well tolerated, some patients experience severe immune-related adverse events (irAEs). Liquid biopsy is a non-invasive diagnostic procedure involving the isolation of circulating biomarkers, such as circulating tumor cells (CTC), cell-free DNA (cfDNA), and microRNAs (miRNAs). Thanks to recent advances in technologies, such as next-generation sequencing (NGS) and digital polymerase chain reaction (dPCR), liquid biopsy has become a useful tool to provide baseline information on the tumor, and to monitor response to treatments. This review highlights the potential role of liquid biomarkers in the selection of NSCLC patients who could respond to immunotherapy, and in the identification of patients who are most likely to experience irAEs, in order to guide improvements in care.

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