Evidence map›Paper›PMID 25864651›Full record

ArticleActa pharmacologica Sinica2015

Amiloride sensitizes human pancreatic cancer cells to erlotinib in vitro through inhibition of the PI3K/AKT signaling pathway.

Yuan-ting Zheng, Hui-ying Yang, Tao Li, Bei Zhao, Teng-fei Shao, Xiao-qiang Xiang, Wei-min Cai

Open access · bronzeAbstract read
In one paragraph

Article in Acta pharmacologica Sinica, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

19 citing papers in PubMed, 32 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

7 authors at 1 institution in 1 country.

Yuan-ting ZhengDepartment of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai 201203, China.
Hui-ying YangDepartment of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai 201203, China.
Tao LiDepartment of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai 201203, China.
Bei ZhaoDepartment of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai 201203, China.
Teng-fei ShaoDepartment of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai 201203, China.
Xiao-qiang XiangDepartment of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai 201203, China.
Wei-min CaiDepartment of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai 201203, China.
Fudan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimBlockade of EGFR by EGFR tyrosine kinase inhibitors such as erlotinib is insufficient for effective treatment of human pancreatic cancer due to independent activation of the Akt pathway, while amiloride, a potassium-sparing diuretic, has been found as a potential Akt inhibitor. The aim of this study was to investigate the anticancer effects of combined amiloride with erlotinib against human pancreatic cancer cells in vitro.

methodsCell proliferation, colony formation, cell cycle and apoptosis were analyzed in 4 human pancreatic cancer cell lines Bxpc-3, PANC-1, Aspc-1 and CFPAC-1 treated with erlotinib or amiloride alone, or in their combination. The synergistic analysis for the effects of combinations of amiloride and erlotinib was performed using Chou-Talalay's combination index isobolographic method.

resultsAmiloride (10, 30, and 100 μmol/L) concentration-dependently potentiated erlotinib-induced inhibition of cell proliferation and colony formation in the 4 pancreatic cancer cell lines. Isobolographic analysis confirmed that combinations of amiloride and erlotinib produced synergistic cytotoxic effects. Amiloride significantly potentiated erlotinib-induced G0/G1 cell-cycle arrest and apoptosis in Bxpc-3 and PANC-1 cells. Amiloride inhibited EGF-stimulated phorsphorylation of AKT, and significantly enhanced erlotinib-induced downregulation of phorsphorylation of EGFR, AKT, PI3K P85 and GSK 3β in Bxpc-3 and PANC-1 cells.

conclusionAmiloride sensitizes human pancreatic cancer cells to erlotinib in vitro through inhibition of the PI3K/AKT signaling pathway. Treatment of pancreatic cancer patients with combination of erlotinib and amiloride merits further investigation.

Indexed as

Phosphoinositide-3 Kinase InhibitorsAmilorideAntineoplastic Combined Chemotherapy ProtocolsApoptosisCell Line, TumorCell ProliferationDose-Response Relationship, DrugDrug SynergismErbB ReceptorsErlotinib HydrochlorideG1 Phase Cell Cycle CheckpointsHumansMolecular Targeted TherapyPancreatic NeoplasmsPhosphatidylinositol 3-KinasePhosphorylationAmilorideEGFR protein, humanErbB ReceptorsErlotinib HydrochloridePhosphatidylinositol 3-KinasePhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-akt

Identifiers

PMID25864651
PMCPMC4422948
OpenAlexW1571940703

What OpenQuestion holds

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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.