Evidence map›Paper›PMID 23320839›Full record

ArticleCancer cell international2013

MEK inhibition induced downregulation of MRP1 and MRP3 expression in experimental hepatocellular carcinoma.

Shibo Lin, Katrin Hoffmann, Zhi Xiao, Nan Jin, Uwe Galli, Elvira Mohr, Markus W Büchler, Peter Schemmer

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

Article in Cancer cell international, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

16 citing papers in PubMed, 27 citations in OpenAlex.

  1. Trial
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  4. Drug-Induced Liver Injury Associated With Emerging Cancer Therapies.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Review
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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

8 authors at 2 institutions in 2 countries.

Shibo Lin *Department of General and Transplant Surgery, Ruprecht-Karls-University, Im Neuenheimer Feld 110, Heidelberg, 69120, Germany.
Katrin Hoffmann *Department of General and Transplant Surgery, Ruprecht-Karls-University, Im Neuenheimer Feld 110, Heidelberg, 69120, Germany.
Zhi XiaoDepartment of Breast Surgery, Xiangya Hospital, Zhongnan University, Changsha, 410008, China.
Nan JinDepartment of Hematology, Oncology, and Rheumatology, Ruprecht-Karls-University, Heidelberg, 69120, Germany.
Uwe GalliDepartment of General and Transplant Surgery, Ruprecht-Karls-University, Im Neuenheimer Feld 110, Heidelberg, 69120, Germany.
Elvira MohrDepartment of General and Transplant Surgery, Ruprecht-Karls-University, Im Neuenheimer Feld 110, Heidelberg, 69120, Germany.
Markus W BüchlerDepartment of General and Transplant Surgery, Ruprecht-Karls-University, Im Neuenheimer Feld 110, Heidelberg, 69120, Germany.
Peter SchemmerDepartment of General and Transplant Surgery, Ruprecht-Karls-University, Im Neuenheimer Feld 110, Heidelberg, 69120, Germany.
Heidelberg University · DECentral South University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

unlabelled

backgroundHepatocellular carcinoma (HCC) exhibits strong intrinsic and acquired drug resistance which is the main obstacle to chemotherapy. Overexpression of ATP binding cassette (ABC) proteins correlates with activation of mitogen activated protein kinase (MAPK) pathway in HCC. Here, we systematically investigated the inhibition of MAPK pathway and its role in regulating HCC cell growth as well as ABC proteins MRP1 and MRP3 expression.

methodsThe Raf1 kinase inhibitor (GW5074) and different MEK inhibitors (U0126 and AZD6244) were used to treat HCC cells to identify their effects on HCC cell growth and ABC proteins expression in vitro. Cell viability tests were performed after the treatment of MAPK pathway inhibitors and in combination with gemcitabine or doxorubicin. Western blot was applied to assess the changes of MAPK pathway and protein expression of MRP1 and MRP3. Flow cytometry was used to measure intracellular doxorubicin accumulation after the treatment of MEK inhibitors.

resultsBoth Raf1 inhibitor (GW5074) and MEK inhibitors (U0126 and AZD6244) suppressed HCC cell growth in a dose dependent manner. Pre-treatment of MEK inhibitor U0126 or AZD6244 sensitized HCC cells to gemcitabine or doxorubicin based chemotherapy. Raf1 inhibitor GW5074 had no effect on MRP1 and MRP3 protein expression. Treatment of gemcitabine or doxorubicin activated phosphorylated ERK and induced the upregulation of MRP1 and MRP3. MEK inhibitors U0126 and AZD6244 deactivated phosphorylated ERK, decreased endogenous MRP1 expression, reversed gemcitabine or doxorubicin induced MRP1 and MRP3 upregulation, and increased the intracellular doxorubicin accumulation.

conclusionThis study provides evidence that MEK inhibitors sensitize HCC cells to chemotherapy by increasing intracellular chemodrug accumulation. MEK inhibirors U0126 and AZD6244 reduced MRP1 as well as MRP3 expression, and may contribute partially to the sensitization. The combination of MEK inhibitor and conventional chemotherapy may offer new therapeutic option for the treatment of resistant HCC.

Identifiers

PMID23320839
PMCPMC3558388
OpenAlexW2170834007

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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.