Evidence map›Paper›PMID 26783187›Full record

ArticleInternational journal of oncology2016

miR-200/ZEB axis regulates sensitivity to nintedanib in non-small cell lung cancer cells.

Nobuhiko Nishijima, Masahiro Seike, Chie Soeno, Mika Chiba, Akihiko Miyanaga, Rintaro Noro, Teppei Sugano, Masaru Matsumoto, Kaoru Kubota, Akihiko Gemma

Open access · hybridAbstract read
In one paragraph

Article in International journal of oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
12.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 83 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Nobuhiko NishijimaDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.
Masahiro SeikeDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.
Chie SoenoDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.
Mika ChibaDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.
Akihiko MiyanagaDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.
Rintaro NoroDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.
Teppei SuganoDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.
Masaru MatsumotoDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.
Kaoru KubotaDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.
Akihiko GemmaDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.
Nippon Medical School · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nintedanib (BIBF1120) is a multi-targeted angiokinase inhibitor and has been evaluated in idiopathic pulmonary fibrosis and advanced non-small cell lung cancer (NSCLC) patients in clinical studies. In the present study, we evaluated the antitumor effects of nintedanib in 16 NSCLC cell lines and tried to identify microRNA (miRNA) associated with sensitivity to nintedanib. No correlations between FGFR, PDGFR and VEGFR family activation and sensitivity to nintedanib were found. The difference in miRNA expression profiles between 5 nintedanib-sensitive and 5 nintedanib-resistant cell lines was evaluated by miRNA array and quantitative RT-PCR analysis (qRT-PCR). Expression of miR-200b, miR-200a and miR-141 belonging to the miR-200 family which contributes to epithelial-mesenchymal transition (EMT), was significantly lower in 5 nintedanib-resistant than in 5 nintedanib-sensitive cell lines. We examined the protein expression of EMT markers in these 10 NSCLC cell lines. E-cadherin expression was lower, and vimentin and ZEB1 expression were higher in 5 nintedanib-resistant cell lines. PC-1 was the most sensitive of the NSCLC cell lines to nintedanib. We established nintedanib-resistant PC-1 cells (PC-1R) by the stepwise method. PC-1R cells also showed decreased expression of miR-200b, miR-141 and miR-429 and increased expression of ZEB1 and ZEB2. We confirmed that induction of miR-200b or miR-141 enhanced sensitivity to nintedanib in nintedanib-resistant A549 and PC1-R cells. In addition, we evaluated the response to gefitinib in combination with nintedanib after TGF-β1 exposure of A549 cells. Nintedanib was able to reverse TGF-β1-induced EMT and resistance to gefitinib caused by miR-200b and miR-141 upregulation and ZEB1 downregulation. These results suggested that the miR-200/ZEB axis might be predictive biomarkers for sensitivity to nintedanib in NSCLC cells. Furthermore, nintedanib combined with gefitinib might be a novel therapeutic strategy for NSCLC cells with EMT phenotype and resistance to gefitinib.

Indexed as

Antineoplastic AgentsBiomarkers, TumorCarcinoma, Non-Small-Cell LungCell Line, TumorDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionGefitinibGene Expression ProfilingHumansIndolesInhibitory Concentration 50Lung NeoplasmsMicroRNAsPhenotypeQuinazolinesReceptor, Platelet-Derived Growth Factor betaAntineoplastic AgentsBiomarkers, TumorGefitinibIndolesMicroRNAsMIRN141 microRNA, humanMIRN200 microRNA, humannintedanibQuinazolinesReceptor, Platelet-Derived Growth Factor betaReceptors, Fibroblast Growth FactorReceptors, Vascular Endothelial Growth FactorZEB1 protein, humanZinc Finger E-box-Binding Homeobox 1

Identifiers

PMID26783187
PMCPMC4750530
OpenAlexW2233226213

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.