Evidence map›Paper›PMID 38609654›Full record

ArticleCancer chemotherapy and pharmacology2024

PARP1 promotes EGFR-TKI drug-resistance via PI3K/AKT pathway in non-small-cell lung cancer.

Xianping Xu, Yu Liu, Qiang Gong, Le Ma, Wei Wei, Linqiong Zhao, Zhibin Luo

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In one paragraph

Article in Cancer chemotherapy and pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
2.1field-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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 5 citations in OpenAlex.

  1. Pooled it
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  6. Review
  7. Article
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 3 institutions in 1 country.

Xianping XuDepartment of Oncology, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang District Luzhou, Sichuan, 646000, China.
Yu LiuDepartment of Oncology, Chongqing Genaral Hospital, No.118, Xingguang Avenue, Liangjiang New Area, Chongqing, 401147, China.
Qiang GongDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Road Street, Shapingba District, Chongqing, 400038, China.
Le MaDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Road Street, Shapingba District, Chongqing, 400038, China.
Wei WeiDepartment of Oncology, Chongqing Genaral Hospital, No.118, Xingguang Avenue, Liangjiang New Area, Chongqing, 401147, China.
Linqiong ZhaoDepartment of Oncology, Chongqing Genaral Hospital, No.118, Xingguang Avenue, Liangjiang New Area, Chongqing, 401147, China.
Zhibin LuoDepartment of Oncology, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang District Luzhou, Sichuan, 646000, China. 18281728124@yeah.net.
First People's Hospital of Chongqing · CNArmy Medical University · CNSouthwest Hospital · CN

Funding

Chongqing Yuzhong District Science and Technology Committee 20190118
6 · The paper itself

Abstract

purposeTyrosine kinase inhibitor (TKI) resistance is the main type of drug resistance in lung cancer patients with epidermal growth factor receptor (EGFR) mutations, but its underlying mechanism remains unclear. The purpose of this work was to investigate the mechanism by which PARP1 regulates EGFR-TKI resistance to identify potential targets for combating drug resistance.

methodsThe GEO databases, TCGA databases, western blot and qPCR studies were used to investigate the expression of PARP1 in lung cancer cells and tissues and its correlation with the prognosis of lung cancer. The expression of PARP1 in lung cancer TKI resistant cell PC9-ER and TKI sensitive cell PC9 was analyzed by qPCR and western blot. After knocking down of PARP1, CCK-8 assays, colony formation, flow cytometry were used to investigate its impact on erlotinib sensitivity, cell survival, cell cycle, and apoptosis. RNA-seq was used to investigate the mechanism by which PARP1 participates in EGFR-TKI resistance, and the results were validated in vitro and in vivo studies.

resultsPARP1 was highly expressed in both lung cancer tissues and cells. Subsequently, increased PARP1 expression was observed in PC9-ER compared with its parental cell line. Knockdown of PARP1 increased erlotinib sensitivity, promoted cell apoptosis, and suppressed cell growth. RNA-seq and previous studies have shown that the PI3K/AKT/mTOR/P70S6K pathway is involved in PARP1-mediated TKI resistance, and these results were confirmed by Western blot in vitro and in vivo.

conclusionPARP1 may serve as a potential therapeutic target for reversing EGFR-TKI resistance in NSCLC via the PI3K/AKT/mTOR/P70S6K pathway.

Indexed as

Carcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmErbB ReceptorsLung NeoplasmsPoly (ADP-Ribose) Polymerase-1Protein Kinase InhibitorsProto-Oncogene Proteins c-aktAnimalsApoptosisCell Line, TumorCell ProliferationErlotinib HydrochlorideHumansMaleMiceMice, NudeEGFR protein, humanErbB ReceptorsErlotinib HydrochloridePARP1 protein, humanPhosphatidylinositol 3-KinasesPoly (ADP-Ribose) Polymerase-1Protein Kinase InhibitorsProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesDrug sensitivityLung cancerPARP1PI3K/AKT/mTOR/P70S6KTyrosine kinase inhibitor

Identifiers

PMID38609654
OpenAlexW4394745078

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Registered trials

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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.