The Effect of Afatinib Treatment in Non-small Cell Lung Cancer Cells

Pancewicz-Wojtkiewicz, Joanna; Bernatowicz, Pawel

doi:10.21873/anticanres.11723

Cited by 4 publications

(1 citation statement)

References 12 publications

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“…According to the International Agency for Research on Cancer(IARC) 2012, the incidence of lung cancer ranks first in the incidence of all malignant tumors 1. Non-small cell lung cancer (NSCLC) is the main type of lung cancer, accounting for about 80% of all lung cancer 2. NSCLC is mainly classified into squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, large cell lung cancer, and sarcomatoid carcinoma.…”

Section: Introductionmentioning

confidence: 99%

<p>Expression and significance of LncRNA MNX1-AS1 in non-small cell lung cancer</p>

Liu

Guo

Zhang

et al. 2019

OTT

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Objective: To investigate the expression of LncRNA MNX1-AS1 in NSCLC and its effect on NSCLC cell lines. Methods: In this experiment, the expression of LncRNA MNX1-AS1 was detected by qRT-PCR in 116 NSCLC samples, and the correlation between MNX1-AS1 and NSCLC patients was further analyzed by chi-square test. The prognostic value of MNX1-AS1 was assessed by Kaplan-Meier survival curve. The expression of MNX1-AS1 in NSCLC cell line A549 was knocked down, and the effects of MNX1-AS1 on proliferation, apoptosis, migration and invasion of NSCLC cells were evaluated. Results: Compared with normal lung tissue, the expression of MNX1-AS1 was significantly increased in lung cancer tissues ( p <0.05). The expression level of MNX1-AS1 in NSCLC cell line A549 was significantly higher than that in human normal lung epithelial cell line Beas-2B ( p <0.05). MNX1-AS1 expression was significantly associated with TNM stage and lymph node metastasis ( p <0.05). Kaplan-Meier survival curve analysis showed that high expression of MNX1-AS1 was associated with a poor prognosis in NSCLC. In addition, knockdown of MNX1-AS1 inhibited proliferation, migration and invasion of the NSCLC cell line A549 and promoted apoptosis. Conclusion: The up-regulation of LncRNA MNX1-AS1 is associated with the progression and prognosis of NSCLC. Knockdown of LncRNA MNX1-AS1 inhibits proliferation, migration and invasion of NSCLC cells and promotes apoptosis.

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Section: Introductionmentioning

confidence: 99%

<p>Expression and significance of LncRNA MNX1-AS1 in non-small cell lung cancer</p>

Liu

Guo

Zhang

et al. 2019

OTT

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Cancer: Therapeutic Approaches Targeting Stress Pathways

Zuehlke

Neckers

2018

Encyclopedia of Life Sciences

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Cell stress is a ubiquitous term covering vast forms of perturbations to the homeostatic state of the cell. The response mechanisms to these types of stresses are aimed at protecting the cells and allowing them to recover from the inflicted damage. Before reaching the critical level of stress resulting in stress‐induced cell death, cells utilise these survival strategies to protect themselves from the exposed insult. Tumour cells similarly utilise these survival strategies to continue replication despite their extreme surrounding environment. Survival responses to stress also allow tumour cells to overcome additional challenges presented by treatment regiments such as chemotherapy and radiation, resulting in resistance. These survival pathways, therefore, are being targeted in addition to standard treatment to force the stressed oncogenic cells into their death pathways. Use of these survival pathway inhibitors has markedly increased tumour sensitivity to chemotherapy and radiation, suggesting an alternative approach to cancer therapeutics. Key Concepts Eukaryotic cells are able to activate multiple stress response pathways when exposed to environmental stress. In cancer cells, these stress response pathways are frequently upregulated to cope with nutrient deprivation, hypoxia, abundance of misfolded proteins, and other stresses common to cancer cells. Many cancer drugs induce cell stress and stimulate one or more cell stress response pathways. Thus, cancer cells use multiple cell stress response pathways to support drug resistance, particularly to cytotoxic agents. Cancer cell sensitivity to cytotoxic drugs may be enhanced by simultaneously blocking cell stress response pathways.

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Stimulation of Eryptosis by Afatinib

Bhuyan

Läng

2018

Cell Physiol Biochem

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Background/Aims: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor afatinib is primarily utilized for the treatment of non-small cell lung carcinoma. The drug is at least partially effective by triggering suicidal tumor cell death. Side effects of afatinib treatment include anemia. At least in theory, afatinib induced anemia could be secondary to stimulation of suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling potentially stimulating eryptosis include increase of cytosolic Ca 2+ activity ([Ca 2+ ] i ), induction of oxidative stress, and increase of ceramide abundance. The present study explored, whether afatinib induces eryptosis and, if so, whether its effect involves Ca 2+ entry, oxidative stress, and/or ceramide. Methods: Flow cytometry was employed to quantify phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca 2+ ] i from Fluo3-fluorescence, reactive oxygen species (ROS) abundance from DCFDA dependent fluorescence, and ceramide abundance utilizing specific antibodies. Results: A 48 hours exposure of human erythrocytes to afatinib (≥ 4 µg/ml) significantly increased the percentage of annexin-V-binding cells and significantly decreased forward scatter. Afatinib significantly increased Fluo3-fluorescence, DCFDA fluorescence and ceramide abundance. The effect of afatinib on annexin-V-binding and forward scatter was significantly blunted by removal of extracellular Ca 2+ . Conclusions: Afatinib triggers phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part due to Ca 2+ entry, oxidative stress, and ceramide.

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The Effect of Afatinib Treatment in Non-small Cell Lung Cancer Cells

Abstract: Advanced analysis, might be helpful in understanding the mechanisms of relations between tyrosine kinase inhibition of EGFR and HSPA5 in lung cancer cells.

Cited by 4 publications

References 12 publications

<p>Expression and significance of LncRNA MNX1-AS1 in non-small cell lung cancer</p>

<p>Expression and significance of LncRNA MNX1-AS1 in non-small cell lung cancer</p>

Cancer: Therapeutic Approaches Targeting Stress Pathways

Stimulation of Eryptosis by Afatinib

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