Evidence map›Paper›PMID 26718641›Full record

ArticleInternational journal of oncology2016

Macrolides sensitize EGFR-TKI-induced non-apoptotic cell death via blocking autophagy flux in pancreatic cancer cell lines.

Shuntaro Mukai, Shota Moriya, Masaki Hiramoto, Hiromi Kazama, Hiroko Kokuba, Xiao-Fang Che, Tomohisa Yokoyama, Satoshi Sakamoto, Akihiro Sugawara, Toshiaki Sunazuka and 4 more

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 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

27 citing papers in PubMed, 46 citations in OpenAlex.

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  4. Oncology letters · 2024
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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

14 authors at 3 institutions in 1 country.

Shuntaro MukaiDepartment of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan.
Shota MoriyaDepartment of Biochemistry, Tokyo Medical University, Tokyo, Japan.
Masaki HiramotoDepartment of Biochemistry, Tokyo Medical University, Tokyo, Japan.
Hiromi KazamaDepartment of Biochemistry, Tokyo Medical University, Tokyo, Japan.
Hiroko KokubaLaboratory of Electron Microscopy, Tokyo Medical University, Tokyo, Japan.
Xiao-Fang CheDepartment of Biochemistry, Tokyo Medical University, Tokyo, Japan.
Tomohisa YokoyamaDepartment of Clinical Oncology, Tokyo Medical University, Tokyo, Japan.
Satoshi SakamotoDepartment of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
Akihiro SugawaraKitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.
Toshiaki SunazukaKitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.
Satoshi ŌmuraKitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.
Hiroshi HandaDepartment of Nanoparticle Translational Research, Tokyo Medical University, Tokyo, Japan.
Takao ItoiDepartment of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan.
Keisuke MiyazawaDepartment of Biochemistry, Tokyo Medical University, Tokyo, Japan.
Tokyo Medical University · JPKitasato University · JPTokyo Institute of Technology · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pancreatic cancer is one of the most difficult types of cancer to treat because of its high mortality rate due to chemotherapy resistance. We previously reported that combined treatment with gefitinib (GEF) and clarithromycin (CAM) results in enhanced cytotoxicity of GEF along with endoplasmic reticulum (ER) stress loading in non-small cell lung cancer cell lines. An epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) such as GEF induces autophagy in a pro-survival role, whereas CAM inhibits autophagy flux in various cell lines. Pronounced GEF-induced cytotoxicity therefore appears to depend on the efficacy of autophagy inhibition. In the present study, we compared the effect on autophagy inhibition among such macrolides as CAM, azithromycin (AZM), and EM900, a novel 12-membered non-antibiotic macrolide. We then assessed the enhanced GEF-induced cytotoxic effect on pancreatic cancer cell lines BxPC-3 and PANC-1. Autophagy flux analysis indicated that AZM is the most effective autophagy inhibitor of the three macrolides. CAM exhibits an inhibitory effect but less than AZM and EM900. Notably, the enhancing effect of GEF-induced cytotoxicity by combining macrolides correlated well with their efficient autophagy inhibition. However, this pronounced cytotoxicity was not due to upregulation of apoptosis induction, but was at least partially mediated through necroptosis. Our data suggest the possibility of using macrolides as 'chemosensitizers' for EGFR-TKI therapy in pancreatic cancer patients to enhance non-apoptotic tumor cell death induction.

Indexed as

Drug SynergismApoptosisAutophagyAzithromycinCell Line, TumorClarithromycinErbB ReceptorsErythromycinGefitinibGene Expression Regulation, NeoplasticHumansMacrolidesPancreatic NeoplasmsQuinazolines(8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin AAzithromycinClarithromycinEGFR protein, humanErbB ReceptorsErythromycinGefitinibMacrolidesQuinazolines

Identifiers

PMID26718641
PMCPMC4734605
OpenAlexW2110198133

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.