Evidence map›Paper›PMID 27530445›Full record

ArticleJournal of cancer research and clinical oncology2016

Endothelin-1 (ET-1) induces resistance to bortezomib in human multiple myeloma cells via a pathway involving the ETB receptor and upregulation of proteasomal activity.

Maria Vaiou, Evanthia Pangou, Panagiotis Liakos, Nikos Sakellaridis, George Vassilopoulos, Konstantinos Dimas, Christos Papandreou

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

Article in Journal of cancer research and clinical oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.6field-weighted citation impact, top 15% 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

6 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Drug Discovery of DKK1 Inhibitors.Frontiers in pharmacology · 2022
    Review
  4. Article
  5. Article
  6. Article
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

7 authors at 1 institution in 1 country.

Maria VaiouDepartment of Medical Oncology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, 41110, Larissa, Greece.
Evanthia PangouLaboratory of Biochemistry, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, 41110, Larissa, Greece.
Panagiotis LiakosLaboratory of Biochemistry, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, 41110, Larissa, Greece.
Nikos SakellaridisDepartment of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, 41110, Larissa, Greece.
George VassilopoulosDepartment of Hematology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, 41110, Larissa, Greece.
Konstantinos DimasDepartment of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, 41110, Larissa, Greece. kdimas@med.uth.gr.ORCID http://orcid.org/0000-0001-7481-9148
Christos PapandreouDepartment of Medical Oncology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, 41110, Larissa, Greece. cpapandreou@med.uth.gr.
University of Thessaly · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeBortezomib (BTZ) is used for the treatment of multiple myeloma (MM). However, a significant proportion of patients may be refractory to the drug. This study aimed to investigate whether the endothelin (ET-1) axis may act as an escape mechanism to treatment with bortezomib in MM cells.

methodsNCI-H929 and RPMI-8226 (human MM cell lines) were cultured with or without ET-1, BTZ, and inhibitors of the endothelin receptors. ET-1 levels were determined by ELISA, while the protein levels of its receptors and of the PI3K and MAPK pathways' components by western blot. Effects of ET-1 on cell proliferation were studied by MTT and on the ubiquitin proteasome pathway by assessing the chymotryptic activity of the 20S proteasome in cell lysates.

resultsEndothelin receptors A and B (ETAR and ETBR, respectively) were found to be expressed in both cell lines, with the RPMI-8226 cells that are considered resistant to BTZ, expressing higher levels of ETBR and in addition secreting ET-1. Treatment of the NCI-H929 cells with ET-1 increased proliferation, while co-incubation of these cells with ET-1 and BTZ decreased BTZ efficacy with concomitant upregulation of 20S proteasomal activity. Si-RNA silencing or chemical blockade of ETBR abrogated the protective effects of ET-1. Finally, data suggest that the predominant signaling pathway involved in ET-1/ETBR-induced BTZ resistance in MM cells may be the MAPK pathway.

conclusionOur data suggest a possible role of the ET-1/ETBR axis in regulating the sensitivity of MM cells to BTZ. Thus, combining bortezomib with strategies to target the ET-1 axis could prove to be a novel promising therapeutic approach in MM.

Indexed as

BortezomibCell Line, TumorDrug Resistance, NeoplasmEndothelin-1Endothelin A Receptor AntagonistsHumansMAP Kinase Signaling SystemMultiple MyelomaPeptides, CyclicPhosphatidylinositol 3-KinasesProteasome Endopeptidase ComplexReceptor, Endothelin AReceptor, Endothelin BUbiquitinBortezomibcyclo(Trp-Asp-Pro-Val-Leu)Endothelin-1Endothelin A Receptor AntagonistsPeptides, CyclicPhosphatidylinositol 3-KinasesProteasome Endopeptidase ComplexReceptor, Endothelin AReceptor, Endothelin BUbiquitinBortezomibEndothelin-1ETBRMultiple myelomaUbiquitin–proteasome pathway

Identifiers

PMID27530445
PMCPMC11819011
OpenAlexW2507448136

What OpenQuestion holds

Textmetadata
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.