Evidence map›Paper›PMID 26497205›Full record

ArticleOncotarget2015

Metformin attenuates gefitinib-induced exacerbation of pulmonary fibrosis by inhibition of TGF-β signaling pathway.

Li Li, Wenting Huang, Kunlin Li, Kejun Zhang, Caiyu Lin, Rui Han, Conghua Lu, Yubo Wang, Hengyi Chen, Fenfen Sun and 1 more

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 1 pooled it
6.7field-weighted citation impact, top 3% 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

59 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 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

11 authors at 2 institutions in 1 country.

Li LiDepartment of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing, China.
Wenting HuangDepartment of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing, China.
Kunlin LiDepartment of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing, China.
Kejun ZhangDepartment of Clinical Labratory, Daping Hospital, Third Military Medical University, Chongqing, China.
Caiyu LinDepartment of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing, China.
Rui HanDepartment of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing, China.
Conghua LuDepartment of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing, China.
Yubo WangDepartment of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing, China.
Hengyi ChenDepartment of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing, China.
Fenfen SunDepartment of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing, China.
Yong HeDepartment of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing, China.
Army Medical University · CNDaping Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Interstitial lung disease (ILD) is a serious side-effect of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment. Therefore, it is necessary to study underlying mechanisms for the development of pulmonary fibrosis induced by EGFR-TKI and potential approaches to attenuate it. Metformin is a well-established and widely prescribed oral hypoglycemic drug, and has gained attention for its potential anticancer effects. Recent reports have also demonstrated its role in inhibiting epithelial-mesenchymal transition and fibrosis. However, it is unknown whether metformin attenuates EGFR-TKI-induced pulmonary fibrosis. The effect of metformin on EGFR-TKI-induced exacerbation of pulmonary fibrosis was examined in vitro and in vivo using MTT, Ki67 incorporation assay, flow cytometry, immunostaining, Western blot analysis, and a bleomycin-induced pulmonary fibrosis rat model. We found that in lung HFL-1 fibroblast cells, TGF-β or conditioned medium from TKI-treated lung cancer PC-9 cells or conditioned medium from TKI-resistant PC-9GR cells, induced significant fibrosis, as shown by increased expression of Collegen1a1 and α-actin, while metformin inhibited expression of fibrosis markers. Moreover, metformin decreased activation of TGF-β signaling as shown by decreased expression of pSMAD2 and pSMAD3. In vivo, oral administration of gefitinib exacerbated bleomycin-induced pulmonary fibrosis in rats, as demonstrated by HE staining and Masson staining. Significantly, oral co-administration of metformin suppressed exacerbation of bleomycin-induced pulmonary fibrosis by gefitinib. We have shown that metformin attenuates gefitinib-induced exacerbation of TGF-β or bleomycin-induced pulmonary fibrosis. These observations indicate metformin may be combined with EGFR-TKI to treat NSCLC patients.

Indexed as

AnimalsAntineoplastic AgentsBleomycinBlotting, WesternEpithelial-Mesenchymal TransitionFlow CytometryGefitinibHumansImmunohistochemistryLung Diseases, InterstitialMaleMetforminPulmonary FibrosisQuinazolinesRatsRats, Sprague-DawleyAntineoplastic AgentsBleomycinGefitinibMetforminQuinazolinesTransforming Growth Factor betaEGFR-TKImetforminpulmonary fibrosisTGF-β

Identifiers

PMID26497205
PMCPMC4791254
OpenAlexW2281067753

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.