Evidence map›Paper›PMID 24901645›Full record

ArticlePloS one2014

HIF-1α inhibition reverses multidrug resistance in colon cancer cells via downregulation of MDR1/P-glycoprotein.

Jianfang Chen, Zhenyu Ding, Yonghai Peng, Feng Pan, Jianjun Li, Lan Zou, Yanling Zhang, Houjie Liang

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

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed
6.5field-weighted citation impact, top 2% 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

94 citing papers in PubMed, 154 citations in OpenAlex.

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34 more citing papers are in PubMed but not listed here.

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 3 institutions in 1 country.

Jianfang ChenDepartment of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
Zhenyu DingDepartment of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China; Department of Oncology, General Hospital of Shenyang Military Region, Shenyang, Liaoning, China.
Yonghai PengDepartment of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
Feng PanDepartment of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
Jianjun LiDepartment of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
Lan ZouDepartment of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
Yanling ZhangDepartment of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
Houjie LiangDepartment of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
Southwest Hospital · CNArmy Medical University · CNGeneral Hospital of Shenyang Military Region · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMultidrug resistance (MDR) is one of the major reasons chemotherapy-based treatments fail. Hypoxia is generally associated with tumor chemoresistance. However, the correlation between the heterodimeric hypoxia-inducible factor-1 (HIF-1) and the multidrug resistance (MDR1) gene/transporter P-glycoprotein (P-gp) remains unclear. This study aims to explore the molecular mechanisms of reversing colon cancer MDR by focusing on the target gene HIF-1α.

methodsA chemotherapeutic sensitivity assay was used to observe the efficiency of MDR reversal in LoVo multicellular spheroids (MCS). The apoptotic level induced by different drugs was examined by flow cytometry (FCM). Binding of HIF-1α to the MDR1 gene promoter was evaluated by Chromatin immunoprecipitation (ChIP). The relationship between HIF-1α/P-gp expression and sensitivity to chemotherapy was analyzed.

resultsThe sensitivity of LoVo MCS to all four chemotherapy drugs was decreased to varying degrees under hypoxic conditions. After silencing the HIF-1α gene, the sensitivities of LoVo MCS to all four chemotherapy drugs were restored. The apoptotic levels that all the drugs induced were all decreased to various extents in the hypoxic group. After silencing HIF-1α, the apoptosis level induced by all four chemotherapy drugs increased. The expression of HIF-1α and P-gp was significantly enhanced in LoVo MCS after treatment with hypoxia. Inhibiting HIF-1α significantly decreased the expression of MDR1/P-gp mRNA or protein in both the LoVo monolayers and LoVo MCS. The ChIP assay showed that HIF-1α was bound to the MDR1 gene promoter. Advanced colon carcinoma patients with expression of both HIF-1α and P-gp were more resistant to chemotherapy than that with non expression.

conclusionsHIF-1α inhibition reverses multidrug resistance in colon cancer cells via downregulation of MDR1/P-gp. The expression of HIF-1α and MDR1/P-gp can be used as a predictive marker for chemotherapy resistance in colon cancer.

Indexed as

Gene Expression Regulation, NeoplasticAntineoplastic AgentsApoptosisATP Binding Cassette Transporter, Subfamily BCell Line, TumorColonic NeoplasmsDrug Resistance, NeoplasmHumansHypoxiaHypoxia-Inducible Factor 1, alpha SubunitPromoter Regions, GeneticProtein BindingRNA InterferenceRNA, MessengerRNA, Small InterferingTranscription, GeneticAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily BHypoxia-Inducible Factor 1, alpha SubunitRNA, MessengerRNA, Small Interfering

Identifiers

PMID24901645
PMCPMC4047061
OpenAlexW1967231442

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.