scholarly journals cIAP1/2 are involved in the radiosensitizing effect of birinapant on NSCLC cell line in vitro

2021 ◽  
Author(s):  
Hao Sun ◽  
Yanan Du ◽  
Ming Yao ◽  
Qin Wang ◽  
Kaihua Ji ◽  
...  
Keyword(s):  
Cell Line ◽  
Nsclc Cell ◽  
Nsclc Cell Line ◽  
Radiosensitizing Effect

scholarly journals Resveratrol raises in vitro anticancer effects of paclitaxel in NSCLC cell line A549 through COX-2 expression

2017 ◽  
Vol 21 (5) ◽  
pp. 465 ◽  
Author(s):  
Fanhua Kong ◽  
Runqi Zhang ◽  
Xudong Zhao ◽  
Guanlin Zheng ◽  
Zhou Wang ◽  
...  
Keyword(s):  
Cell Line ◽  
Nsclc Cell ◽  
Nsclc Cell Line ◽  
Anticancer Effects ◽  
Cox 2

Interferon gamma resistance in setting of LKB1 loss: Phenotypic characterization and investigation of mechanism.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21015-e21015
Author(s):  
Jacob Kaufman
Keyword(s):  
T Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Interferon Gamma ◽  
Checkpoint Inhibitors ◽  
Differentially Expressed Gene ◽  
Nsclc Cell ◽  
Phenotypic Characterization ◽  
Nsclc Cell Line

e21015 Background: NSCLC Patients with LKB1 loss respond poorly to immune checkpoint inhibitors (ICI). Determining mechanisms of the underlying immune resistance and strategies to overcome it are urgent and unmet clinical needs. Methods: We re-expressed WT LKB1 into LKB1 mutant NSCLC cell lines and measured effects on immune associated phenotypes in vitro. Specifically, we evaluated response to exogenous interferon gamma (IFNG), as well T-cell mediated cytotoxicity using a T-cell co-culture assay. To identify IFNG signaling changes influenced by LKB1, we evaluated the differential effects of LKB1 on IFNG induced gene expression using RNAseq. Finally, we performed a whole genome loss of function screen using CRISPR-Cas9 library (TKOv3) to identify genes and pathways that modify susceptibility to IFNG in the LKB1 mutant and LKB1 WT state in the A549 cell line. Results: Across multiple LKB1 mutant cell lines, restoration of WT LKB1 enhanced anti-proliferative effects of IFNG in vitro. Furthermore, WT LKB1 enhanced T-cell mediated cytotoxicity in T-cell co-culture assays using anti-NY-ESO TCR and expression of NY-ESO antigen into an HLA matched NSCLC cell line, H2023 (17% vs 40% cell death; P < 0.01). IFNG treatment induced expression of a core set of interferon-driven genes in both the mutant and LKB1 WT state. However, differentially expressed gene classes included downregulation of proliferation-associated genes in the LKB1 WT state, as well as upregulation of ferroptosis genes, and enhanced IFNG-driven expression of immune evasion genes including PDL1, PDL2, TRAF1, and IDO1 in the LKB1 WT state. PDL1 expression was assessed by flow cytometry and found to be upregulated upon expression of LKB1. Our functional genomics screen identified genes whose inhibition enhanced IFNG susceptibility in the A549 mutant state, and genes whose inhibition restored IFNG resistance in the A549 LKB1 WT state. Preliminary analysis identifies candidate signaling and metabolic pathways that appear to confer IFNG sensitivity in the mutant state without significant effect on IFNG sensitivity after LKB1 add-back. These include modifiers of the Hippo/YAP pathway as well as modifiers of ferroptosis, which will form the basis for further mechanistic experiments. Conclusions: ICI resistance caused by LKB1 loss is associated with insensitivity to IFNG, and can be modified in vitro by re-expression of WT LKB1. An integrated approach to evaluate modifiers of IFNG effects identifies resistance mechanisms that may be potential therapeutic targets.

scholarly journals Tin Mesoporphyrin Selectively Reduces Non-Small-Cell Lung Cancer Cell Line A549 Proliferation by Interfering with Heme Oxygenase and Glutathione Systems

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 917
Author(s):  
Valeria Sorrenti ◽  
Agata Grazia D’Amico ◽  
Ignazio Barbagallo ◽  
Valeria Consoli ◽  
Salvo Grosso ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Line ◽  
Heme Oxygenase ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Antioxidant Systems ◽  
Nsclc Cell Line ◽  
Small Cell Lung

In order to maintain redox homeostasis, non-small-cell lung cancer (NSCLC) increases the activation of many antioxidant systems, including the heme-oxygenase (HO) system. The overexpression of HO-1 has been often associated with chemoresistance and tumor aggressiveness. Our results clearly showed an overexpression of the HO-1 protein in A549 NSCLC cell lines compared to that in non-cancerous cells. Thus, we hypothesized that “off-label” use of tin mesoporphyrin, a well-known HO activity inhibitor clinically used for neonatal hyperbilirubinemia, has potential use as an anti-cancer agent. The pharmacological inhibition of HO activity caused a reduction in cell proliferation and migration of A549. SnMP treatment caused an increase in oxidative stress, as demonstrated by the upregulation of reactive oxygen species (ROS) and the depletion of glutathione (GSH) content. To support these data, Western blot analysis was performed to analyze glucose-6-phosphate dehydrogenase (G6PD), TP53-induced glycolysis and the apoptosis regulator (TIGAR), and the glutamate cysteine ligase catalytic (GCLC) subunit, as they represent the main regulators of the pentose phosphate pathway (PPP) and glutathione synthesis, respectively. NCI-H292, a subtype of the NSCLC cell line, did not respond to SnMP treatment, possibly due to low basal levels of HO-1, suggesting a cellular-dependent antitumorigenic effect. Altogether, our results suggest HO activity inhibition may represent a potential target for selective chemotherapy in lung cancer subtypes.

scholarly journals AURKA upregulation plays a role in fibroblast-reduced gefitinib sensitivity in the NSCLC cell line HCC827

2015 ◽  
Vol 33 (4) ◽  
pp. 1860-1866 ◽  
Author(s):  
JIA CHEN ◽  
HUIQI LU ◽  
WANG ZHOU ◽  
HUABIN YIN ◽  
LISHUANG ZHU ◽  
...  
Keyword(s):  
Cell Line ◽  
Nsclc Cell ◽  
Nsclc Cell Line

scholarly journals Constitutive Cell Proliferation Regulating Inhibitor of Protein Phosphatase 2A (CIP2A) Mediates Drug Resistance to Erlotinib in an EGFR Activating Mutated NSCLC Cell Line

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 716
Author(s):  
Hisham Saafan ◽  
Ahmad Alahdab ◽  
Robin Michelet ◽  
Linus Gohlke ◽  
Janine Ziemann ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Drug Resistance ◽  
Cell Line ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Nsclc Cell ◽  
Egfr Mutations ◽  
Nsclc Cell Line ◽  
Acquired Drug Resistance ◽  
Phosphatase 2A

Exploring mechanisms of drug resistance to targeted small molecule drugs is critical for an extended clinical benefit in the treatment of non-small cell lung cancer (NSCLC) patients carrying activating epidermal growth factor receptor (EGFR) mutations. Here, we identified constitutive cell proliferation regulating inhibitor of protein phosphatase 2A (CIP2A) in the HCC4006rErlo0.5 NSCLC cell line adapted to erlotinib as a model of acquired drug resistance. Constitutive CIP2A resulted in a constitutive activation of Akt signaling. The proteasome inhibitor bortezomib was able to reduce CIP2A levels, which resulted in an activation of protein phosphatase 2A and deactivation of Akt. Combination experiments with erlotinib and bortezomib revealed a lack of interaction between the two drugs. However, the effect size of bortezomib was higher in HCC4006rErlo0.5, compared to the erlotinib-sensitive HCC4006 cells, as indicated by an increase in Emax (0.911 (95%CI 0.867–0.954) vs. 0.585 (95%CI 0.568–0.622), respectively) and decrease in EC50 (52.4 µM (95%CI 46.1–58.8 µM) vs. 73.0 µM (95%CI 60.4–111 µM), respectively) in the concentration–effect model, an earlier onset of cell death induction, and a reduced colony surviving fraction (0.38 ± 0.18 vs. 0.95 ± 0.25, respectively, n = 3, p < 0.05). Therefore, modulation of CIP2A with bortezomib could be an interesting approach to overcome drug resistance to erlotinib treatment in NSCLC.

Generation of Osimertinib-Resistant Cells from EGFR L858R/T790M Mutant NSCLC Cell Line

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Nalini Devi Verusingam ◽  
Yi-Chen Chen ◽  
Heng-Fu Lin ◽  
Chao-Yu Liu ◽  
Ming-Cheng Lee ◽  
...  
Keyword(s):  
Cell Line ◽  
Nsclc Cell ◽  
Nsclc Cell Line ◽  
Resistant Cells

scholarly journals miR-101 sensitizes A549 NSCLC cell line to CDDP by activating caspase 3-dependent apoptosis

2013 ◽  
Vol 7 (2) ◽  
pp. 461-465 ◽  
Author(s):  
JIQING YIN ◽  
MINGGUO WANG ◽  
CUIXIANG JIN ◽  
QINGGUO QI
Keyword(s):  
Cell Line ◽  
Caspase 3 ◽  
Nsclc Cell ◽  
Nsclc Cell Line

scholarly journals Contribution of Neuropilin-1 in Radiation-Survived Subclones of NSCLC Cell Line H1299

2021 ◽  
Vol 43 (3) ◽  
pp. 1203-1211
Author(s):  
Kaori Tsutsumi ◽  
Ayaka Chiba ◽  
Yuta Tadaki ◽  
Shima Minaki ◽  
Takahito Ooshima ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Motility ◽  
Cell Line ◽  
Tumor Cells ◽  
Tube Formation ◽  
Nsclc Cell ◽  
Nsclc Cell Line ◽  
Migration Assay ◽  
Lung Cancer Patients ◽  
Neuropilin 1

Non-small cell lung cancer (NSCLC) is an aggressive lung cancer accounting for approximately 85% of all lung cancer patients. For the patients with Stages IIIA, IIIB, and IIIC, the 5-year survival is low though with the combination with radiotherapy and chemotherapy. In addition, the occurrence of tumor cells (repopulated tumors) that survive irradiation remains a challenge. In our previous report, we subcloned the radiation-surviving tumor cells (IR cells) using the human NSCLC cell line, H1299, and found that the expression of neuropilin-1 (NRP-1) was upregulated in IR cells by the microarray analysis. Here, we investigated the contribution of neuropilin-1 to changes in the characteristics of IR cells. Although there were no differences in angiogenic activity in the tube formation assay between parental and IR cells, the cell motility was increased in IR cells compared to parental cells in the cell migration assay. This enhanced cell motility was suppressed by pretreatment with anti-NRP-1 antibody. Although further studies are necessary to identify other molecules associated with NRP-1, the increase in cellular motility in IR cells might be due to the contribution of NRP-1. Inhibition of NRP-1 would help control tumor malignancy in radiation-surviving NSCLC.

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