Evidence map›Paper›PMID 35280680›Full record

ArticleInternational journal of biological sciences2022

Inhibition of PKM2 Enhances Sensitivity of Olaparib to Ovarian Cancer Cells and Induces DNA Damage.

Sichun Zhou, Duo Li, Di Xiao, Tianyu Wu, Xin Hu, Yu Zhang, Jun Deng, Jing Long, Simeng Xu, Jingtao Wu and 3 more

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

Article in International journal of biological sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
4.2field-weighted citation impact, top 4% 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

25 citing papers in PubMed, 42 citations in OpenAlex.

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  14. Interplay between altered metabolism and DNA damage and repair in ovarian cancer.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024
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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

13 authors at 2 institutions in 1 country.

Sichun ZhouKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, 410013, China; Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, 264005, China.
Duo LiKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, 410013, China; Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, 264005, China.
Di XiaoKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, 410013, China; Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, 264005, China.
Tianyu WuDepartment of Oncology, The Affiliated Zhuzhou Hospital of Xiangya School of Medicine, Central South University, Zhuzhou, 412007, China; Obstetrics and Gynecology Department, Xiangya Hospital, Central South University, Changsha, 410008, China; Departments of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, China.
Xin HuKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, 410013, China; Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, 264005, China.
Yu ZhangDepartment of Oncology, The Affiliated Zhuzhou Hospital of Xiangya School of Medicine, Central South University, Zhuzhou, 412007, China; Obstetrics and Gynecology Department, Xiangya Hospital, Central South University, Changsha, 410008, China; Departments of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, China.
Jun DengKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, 410013, China; Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, 264005, China.
Jing LongDepartment of Oncology, The Affiliated Zhuzhou Hospital of Xiangya School of Medicine, Central South University, Zhuzhou, 412007, China; Obstetrics and Gynecology Department, Xiangya Hospital, Central South University, Changsha, 410008, China; Departments of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, China.
Simeng XuKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, 410013, China; Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, 264005, China.
Jingtao WuKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, 410013, China; Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, 264005, China.
Gaofeng LiDepartment of Oncology, The Affiliated Zhuzhou Hospital of Xiangya School of Medicine, Central South University, Zhuzhou, 412007, China; Obstetrics and Gynecology Department, Xiangya Hospital, Central South University, Changsha, 410008, China; Departments of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, China.
Mei PengDepartment of Oncology, The Affiliated Zhuzhou Hospital of Xiangya School of Medicine, Central South University, Zhuzhou, 412007, China; Obstetrics and Gynecology Department, Xiangya Hospital, Central South University, Changsha, 410008, China; Departments of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, China.
Xiaoping YangKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, 410013, China; Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, 264005, China.
Hunan Normal University · CNCentral South University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Poly (ADP-ribose) polymerase inhibitors (PARPi) have showed clinical benefit as maintenance therapy in advanced ovarian cancer by impairing the homologous recombination (HR) pathway. Pyruvate kinase M2 (PKM2), the significant cancer metabolic biomarker, integrates with DNA damage to directly promote HR. We aimed to investigate the role and molecular mechanism of PKM2 downregulation on sensitization of ovarian cancer cells to PARPi. Inhibitory effects in vitro were assessed by cell viability, clone formation, transwell assay, and flow cytometry. Downregulation of PKM2 by siRNA or small molecular inhibitor shikonin (Sk) enhanced anti-tumour activity of olaparib (Ola) in ovarian cancer cells. Silencing PKM2 or Sk synergized with Ola and reduced cell growth, colony formation and migration, and induced apoptosis. Western blot and immunofluorescence demonstrated that inhibition of PKM2 amplified Ola-induced γH2AX and phospho-ATM (p-ATM) activation and interfered with BRCA1 accumulation in the nucleus. A xenograft animal model demonstrated in vivo antitumor combination effect of Sk and Ola. Furthermore, Western blot and immunofluorenscent analyses of tissue samples revealed that treatment of Sk increased DNA damage, reduced expression of BRCA1 and PKM2. Therefore, this study identified that PKM2 downregulation is a novel therapeutic strategy to enhance Ola effectiveness in treating ovarian cancer.

Indexed as

Ovarian NeoplasmsPyruvate KinaseAnimalsCarcinoma, Ovarian EpithelialCell Line, TumorDNA DamageDrug SynergismFemaleHumansPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsolaparibPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsPyruvate KinaseDNA damagehomologous recombinationolaparibovarian cancerPKM2

Identifiers

PMID35280680
PMCPMC8898351
OpenAlexW4210807284

What OpenQuestion holds

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LicenceCC BY
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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.