Evidence map›Paper›PMID 27411790›Full record

ArticleBMC cancer2016

EHD1 confers resistance to cisplatin in non-small cell lung cancer by regulating intracellular cisplatin concentrations.

Jing Gao, Qingwei Meng, Yanbin Zhao, Xuesong Chen, Li Cai

Open access · goldAbstract readComparative Study
In one paragraph

Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

14 citing papers in PubMed, 28 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

5 authors at 3 institutions in 1 country.

Jing GaoThe Fourth Department of Medicine Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150040, China.
Qingwei MengThe Fourth Department of Medicine Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150040, China.
Yanbin ZhaoThe Fourth Department of Medicine Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150040, China.
Xuesong ChenThe Fourth Department of Medicine Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150040, China.
Li CaiThe Fourth Department of Medicine Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150040, China. caili@ems.hrbmu.edu.cn.
Fourth Affiliated Hospital of Harbin Medical University · CNHarbin Medical University · CNThird Affiliated Hospital of Harbin Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNon-small cell lung cancer (NSCLC) is one of the most aggressive types of cancer. However, resistance to cisplatin (CDDP) remains a major challenge in NSCLC treatment. The purpose of this study was to investigate the ability of EHD1 [Eps15 homology (EH) domain - containing protein 1] to confer CDDP resistance in NSCLC cells and to investigate mechanisms of this resistance.

methodsThe associations between EHD1 expression in NSCLC specimens and clinicopathological features, including prognosis, were assessed by immunohistochemistry (IHC). Using DNA microarrays, we performed a genome-wide analysis of cisplatin-resistant NSCLC cells to identify the involvement of the EHD1 gene in this resistance. We overexpressed and knocked down EHD1 in cell lines to investigate the effect of this gene on proliferation and apoptosis. A quantitative analytical method for assessing CDDP in cells was developed. High-performance liquid chromatography was used to measure the concentration of cisplatin in cells.

resultsThe immunohistochemistry assay showed that adjuvant chemotherapy-treated NSCLC patients expressing EHD1 exhibited reduced OS compared with patients who did not express EHD1 (P = 0.01). Moreover, DNA microarrays indicated that the EHD1 gene was upregulated in CDDP- resistant NSCLC cells. The IC50 value of CDDP in cells that overexpressed EHD1 was 3.3-fold greater than that in the A549-control line, and the IC50 value of EHD1 knockdown cells was at least 5.2-fold lower than that of the control cells, as evidenced by a CCK-8 assay. We found that the percentage of early apoptotic cells was significantly decreased in A549-EHD1 cells, but the rates of early apoptosis were higher in the EHD1 knockdown cell line than in the A549/DDP control line, as indicated by a flow cytometry analysis. High-performance liquid chromatography (HPLC) showed that the total platinum level was lower in A549-EHD1 cells than in control cells, and the concentration of CDDP was higher in the EHD1 knockdown cells than in the A549/DDP control cells.

conclusionWe conclude that EHD1 is required for tumour growth and that it is a regulator of CDDP accumulation and cytotoxicity. The selective knockdown of EHD1 in tumours offers a strategy for enhancing the efficacy of CDDP.

Indexed as

A549 CellsAntineoplastic AgentsApoptosisCarcinoma, Non-Small-Cell LungCell ProliferationChemotherapy, AdjuvantChromatography, High Pressure LiquidCisplatinCytoplasmDrug Resistance, NeoplasmFemaleGene Expression ProfilingGene Knockdown TechniquesHumansImmunohistochemistryInhibitory Concentration 50Antineoplastic AgentsCisplatinEHD1 protein, humanVesicular Transport ProteinsCDDP-resistantEHD1Intracellular concentrationsNSCLC

Identifiers

PMID27411790
PMCPMC4944258
OpenAlexW2463195918

What OpenQuestion holds

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LicenceCC BY
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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.