Evidence map›Paper›PMID 26801746›Full record

ArticleCancer letters2016

Overcoming cisplatin resistance of ovarian cancer cells by targeting HIF-1-regulated cancer metabolism.

Zhihong Ai, Yang Lu, Songbo Qiu, Zhen Fan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.

0numbers the graph read from it
0cells of the map it votes in
108citing papers in PubMed
6.8field-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

108 citing papers in PubMed, 189 citations in OpenAlex.

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48 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

4 authors at 2 institutions in 2 countries.

Zhihong AiDepartment of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yang LuDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Songbo QiuDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Zhen FanDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: zfan@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USShanghai Jiao Tong University · CN

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
A novel targeted therapy for HNSCC based on a novel activity of cetuximabR01CA179015 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI FAN, ZHEN · 2014 to 2018
$1.7M
Mechanisms of tumor resistance to anti-HER/ErbB therapeuticsR01CA129036 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI FAN, ZHEN · 2008 to 2012
$1.6M
NCI NIH HHS CA016672NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA129036NCI NIH HHS R01 CA179015
6 · The paper itself

Abstract

Cisplatin is currently one of the most effective chemotherapeutic drugs used for treating ovarian cancer; however, resistance to cisplatin is common. In this study, we explored an experimental strategy for overcoming cisplatin resistance of human ovarian cancer from the new perspective of cancer cell metabolism. By using two pairs of genetically matched cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines, we tested the hypothesis that downregulating hypoxia-inducible factor-1 (HIF-1), which regulates metabolic enzymes involved in glycolysis, is a promising strategy for overcoming cisplatin resistance of human ovarian cancer cells. We found that cisplatin downregulated the level of the regulatable α subunit of HIF-1, HIF-1α, in cisplatin-sensitive ovarian cancer cells through enhancing HIF-1α degradation but did not downregulate HIF-1α in their cisplatin-resistant counterparts. Overexpression of a degradation-resistant HIF-1α (HIF-1α ΔODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1α or pharmacological promotion of HIF-1α degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. We further demonstrated that knockdown of HIF-1α improved the response of cisplatin-resistant ovarian cancer cells to cisplatin by redirecting the aerobic glycolysis in the resistant cancer cells toward mitochondrial oxidative phosphorylation, leading to cell death through overproduction of reactive oxygen species. Our findings suggest that the HIF-1α-regulated cancer metabolism pathway could be a novel target for overcoming cisplatin resistance in ovarian cancer.

Indexed as

Drug Resistance, NeoplasmAntineoplastic AgentsApoptosisCell Line, TumorCisplatinDose-Response Relationship, DrugDown-RegulationFemaleGene Knockdown TechniquesGlycolysisHumansHypoxia-Inducible Factor 1, alpha SubunitIsoenzymesLactate Dehydrogenase 5L-Lactate DehydrogenaseMitochondriaAntineoplastic AgentsCisplatinHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitIsoenzymesLactate Dehydrogenase 5L-Lactate DehydrogenaseReactive Oxygen SpeciesCancer metabolismCisplatinHIF-1Ovarian cancerResistance

Identifiers

PMID26801746
PMCPMC4769873
OpenAlexW2277854123

What OpenQuestion holds

Textmetadata
LicenceTDM
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.