Prediction of the Mechanisms by Which Quercetin Enhances Cisplatin Action in Cervical Cancer: A Network Pharmacology Study and Experimental Validation

Ji, Huihui; Li, Kehan; Xu, Wenbin; Li, Ruyi; Xie, Shangdan; Zhu, Xueqiong

doi:10.3389/fonc.2021.780387

Cited by 14 publications

(9 citation statements)

References 64 publications

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“…Our KEGG pathway analysis revealed that these targets were significantly enriched in a variety of cancer pathways, platinum drug resistance, and apoptosis pathways, interesting areas for further research. Notably, recent research found that quercetin could overcome CDDP resistance in cervical cancer cells [ 62 ]. Additionally, our previous research found that ECM can sensitize NSCLC cells to CDDP and hypersensitize CDDP-induced apoptosis in NSCLC, but the underlying mechanism was unclear [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Centipeda minima active components and mechanisms in lung cancer

Gao

Pan

et al. 2023

BMC Complement Med Ther

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Background Traditional Chinese medicine (TCM) has been extensively used for neoplasm treatment and has provided many promising therapeutic candidates. We previously found that Centipeda minima (C. minima), a Chinese medicinal herb, showed anti-cancer effects in lung cancer. However, the active components and underlying mechanisms remain unclear. In this study, we used network pharmacology to evaluate C. minima active compounds and molecular mechanisms in lung cancer. Methods We screened the TCMSP database for bioactive compounds and their corresponding potential targets. Lung cancer-associated targets were collected from Genecards, OMIM, and Drugbank databases. We then established a drug-ingredients-gene symbols-disease (D-I-G-D) network and a protein–protein interaction (PPI) network using Cytoscape software, and we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses using R software. To verify the network pharmacology results, we then performed survival analysis, molecular docking analysis, as well as in vitro and in vivo experiments. Results We identified a total of 21 C. minima bioactive compounds and 179 corresponding targets. We screened 804 targets related to lung cancer, 60 of which overlapped with C. minima. The top three candidate ingredients identified by D-I-G-D network analysis were quercetin, nobiletin, and beta-sitosterol. PPI network and core target analyses suggested that TP53, AKT1, and MYC are potential therapeutic targets. Moreover, molecular docking analysis confirmed that quercetin, nobiletin, and beta-sitosterol, combined well with TP53, AKT1, and MYC respectively. In vitro experiments verified that quercetin induced non-small cell lung cancer (NSCLC) cell death in a dose-dependent manner. GO and KEGG analyses found 1771 enriched GO terms and 144 enriched KEGG pathways, including a variety of cancer related pathways, the IL-17 signaling pathway, the platinum drug resistance pathway, and apoptosis pathways. Our in vivo experimental results confirmed that a C. minima ethanol extract (ECM) enhanced cisplatin (CDDP) induced cell apoptosis in NSCLC xenografts. Conclusions This study revealed the key C. minima active ingredients and molecular mechanisms in the treatment of lung cancer, providing a molecular basis for further C. minima therapeutic investigation.

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Section: Discussionmentioning

confidence: 99%

Centipeda minima active components and mechanisms in lung cancer

Gao

Pan

et al. 2023

BMC Complement Med Ther

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“…PD-L1 (1:1,000; ab213524; Abcam), YTHDF1 (1:1,000; ab230330; Abcam), METTL16 (1:300; orb679493; Biorbyt), ZC3H13 (1:1,000; ab70802; Abcam), and GAPDH (1:3,000; AB-M-M 001; GoodHere Technology) were purchased and used in this study. The Western blotting analysis was performed as described before (20).…”

Section: Western Blot Analysismentioning

confidence: 99%

Comprehensive characterization of tumor microenvironment and m6A RNA methylation regulators and its effects on PD-L1 and immune infiltrates in cervical cancer

Zhang

Liu

et al. 2022

Front. Immunol.

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Understanding the role of N6-adenosine methylation (m6A) in the tumor microenvironment (TME) is important since it can contribute to tumor development. However, the research investigating the association between m6A and TME and cervical cancer is still in its early stages. The aim of this study was to discover the possible relationship between m6A RNA methylation regulators, TME, PD-L1 expression levels, and immune infiltration in cervical cancer. We gathered RNA-seq transcriptome data and clinical information from cervical cancer patients using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. To begin, researchers assessed the differences in m6A regulatory factor expression levels between cervical cancer and normal tissues. Clustering analysis was adapted to assess PD-L1 expression, immunological score, immune cell infiltration, TME, and probable pathways in cervical cancer samples. The majority of m6A regulators were found to be considerably overexpressed in cervical cancer tissues. Using consensus clustering of 21 m6A regulators, we identified two subtypes (clusters 1/2) of cervical cancer, and we found that WHO stage and grade were associated with the subtypes. PD-L1 expression increased dramatically in cervical cancer tissues and was significantly linked to ALKBH5, FTO, METTL3, RBM15B, YTHDF1, YTHDF3, and ZC3H13 expression levels. Plasma cells and regulatory T cells (Tregs) were considerably elevated in cluster 2. Cluster 1 is involved in numerous signature pathways, including basal transcription factors, cell cycle, RNA degradation, and the spliceosome. The prognostic signature-based riskscore (METTL16, YTHDF1, and ZC3H13) was found to be an independent prognostic indicator of cervical cancer. The tumor immune microenvironment (TIME) was linked to m6A methylation regulators, and changes in their copy number will affect the quantity of tumor-infiltrating immune cells dynamically. Overall, our research discovered a powerful predictive signature based on m6A RNA methylation regulators. This signature correctly predicted the prognosis of cervical cancer patients. The m6A methylation regulator could be a critical mediator of PD-L1 expression and immune cell infiltration, and it could have a significant impact on the TIME of cervical cancer.

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“…Network pharmacology provides a comprehensive viewpoint, enabling an investigation of the complex network of interactions among the discovered phytochemicals and various targets within the framework of cervical cancer-related pathways. 9,10 …”

Section: Introductionmentioning

confidence: 99%