Evidence map›Paper›PMID 39702296›Full record

ArticleEuropean journal of medical research2024

Shikonin induces the apoptosis and pyroptosis of EGFR-T790M-mutant drug-resistant non-small cell lung cancer cells via the degradation of cyclooxygenase-2.

Shaoyi Cao, Huaqiu Li, Xiaoyan Ye, Xinxing Xing, Yonghuan Xie, Xiangfeng Zeng, Hongjiao Liu, Xing Zhong, Xinyi Yang, Wenxiu Xing and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of medical research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  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

12 authors.

Shaoyi Cao *Department of Immunology and Microbiology, College of Life Science and Technology, MOE Key Laboratory of Tumor Molecular Biology, Jinan University, No. 601 Huangpu Avenue West, Tianhe, Guangzhou, 510632, China.
Huaqiu Li *Department of Immunology and Microbiology, College of Life Science and Technology, MOE Key Laboratory of Tumor Molecular Biology, Jinan University, No. 601 Huangpu Avenue West, Tianhe, Guangzhou, 510632, China.
Xiaoyan Ye *Department of Immunology and Microbiology, College of Life Science and Technology, MOE Key Laboratory of Tumor Molecular Biology, Jinan University, No. 601 Huangpu Avenue West, Tianhe, Guangzhou, 510632, China.
Xinxing XingDepartment of Immunology and Microbiology, College of Life Science and Technology, MOE Key Laboratory of Tumor Molecular Biology, Jinan University, No. 601 Huangpu Avenue West, Tianhe, Guangzhou, 510632, China.
Yonghuan XieDepartment of Immunology and Microbiology, College of Life Science and Technology, MOE Key Laboratory of Tumor Molecular Biology, Jinan University, No. 601 Huangpu Avenue West, Tianhe, Guangzhou, 510632, China.
Xiangfeng ZengDepartment of Immunology and Microbiology, College of Life Science and Technology, MOE Key Laboratory of Tumor Molecular Biology, Jinan University, No. 601 Huangpu Avenue West, Tianhe, Guangzhou, 510632, China.
Hongjiao LiuGuangzhou Women and Children's Medical Center, Guangzhou Medical University, No. 9 Jinsui Road, Zhujiang New Town, Tianhe, Guangzhou, 510623, China.
Xing ZhongThe First Clinical Medical College, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
Xinyi YangDepartment of Immunology and Microbiology, College of Life Science and Technology, MOE Key Laboratory of Tumor Molecular Biology, Jinan University, No. 601 Huangpu Avenue West, Tianhe, Guangzhou, 510632, China.
Wenxiu XingDepartment of Immunology and Microbiology, College of Life Science and Technology, MOE Key Laboratory of Tumor Molecular Biology, Jinan University, No. 601 Huangpu Avenue West, Tianhe, Guangzhou, 510632, China.
Cairong ZhuGuangzhou Women and Children's Medical Center, Guangzhou Medical University, No. 9 Jinsui Road, Zhujiang New Town, Tianhe, Guangzhou, 510623, China. zhucr868@sohu.com.
Xiaoping WuDepartment of Immunology and Microbiology, College of Life Science and Technology, MOE Key Laboratory of Tumor Molecular Biology, Jinan University, No. 601 Huangpu Avenue West, Tianhe, Guangzhou, 510632, China. twxp@jnu.edu.cn.

Funding

Guangdong Basic and Applied Basic Research Foundation of China 2021A1515011184Guangzhou Science and Technology Plan Project 202102010063National Natural Science Foundation of China 82274145
6 · The paper itself

Abstract

backgroundThe T790M mutation in the epidermal growth factor receptor (EGFR) gene is the primary cause of resistance to EGFR-tyrosine kinase inhibitor (TKI) therapy in non-small cell lung cancer (NSCLC) patients. Previous research demonstrated that certain traditional Chinese medicine (TCM) monomers exhibit anti-tumor effects against various malignancies. This study aims to investigate the potentials of shikonin screened from a TCM monomer library containing 1060 monomers in killing EGFR-T790M drug-resistant NSCLC cells and elucidate the underlying mechanisms.

methodsMTT method was used to screen for the TCM monomers with significant killing effects on H1975 cells carrying the EGFR-T790M mutation. The influences of the identified monomer shikonin on cell growth were determined by the colony formation assay. Annexin-V/PI staining and JC-1 staining were applied to detect the effects of shikonin on cell apoptosis. The influences of shikonin on cell membrane integrity were detected by lactate dehydrogenase (LDH) release assay. Reactive oxygen species (ROS) generation was analyzed using DCFH-DA as probe. The mechanisms of shikonin affecting the stability of cyclooxygenase-2 (COX-2) were evaluated by using specific inhibitors for protein degradation pathways. Western blotting was performed to assess the effects of the alteration of COX-2 expression or enzymatic activity on the related signal pathways as well as the apoptotic and pyroptotic markers.

resultsShikonin was identified as a potent cytotoxic compound against EGFR-T790M-mutant NSCLC cells. Shikonin induced cell apoptosis and pyroptosis by triggering the activation of the caspase cascade and cleavage of poly (ADP-ribose) polymerase and gasdermin E by elevating intracellular ROS levels. Further investigations revealed that shikonin induced the degradation of COX-2 via the proteasome pathway, thereby decreasing COX-2 protein level and enzymatic activity and subsequently inhibiting the downstream PDK1/Akt and Erk1/2 signaling pathways through the induction of ROS production. Notably, COX-2 overexpression attenuated shikonin-induced apoptosis and pyroptosis, whereas COX-2 inhibition with celecoxib enhanced the cytotoxic effects of shikonin.

conclusionsCombination treatment with shikonin and COX-2 inhibitor may be a suitable therapeutic strategy for EGFR-T790M-mutant NSCLC treatment.

Indexed as

ApoptosisCarcinoma, Non-Small-Cell LungCyclooxygenase 2Drug Resistance, NeoplasmErbB ReceptorsLung NeoplasmsNaphthoquinonesPyroptosisCell Line, TumorHumansMutationCyclooxygenase 2EGFR protein, humanErbB ReceptorsNaphthoquinonesPTGS2 protein, humanshikoninApoptosisCyclooxygenase-2 (COX-2)Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistancePyroptosisShikonin

Identifiers

PMID39702296
PMCPMC11661004

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.