Target Analysis and Mechanism of Podophyllotoxin in the Treatment of Triple-Negative Breast Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32848800", "kind": "science-record", "revision": 6, "content_hash": "sha256:3369b70cdd89ab4464eeb8ab18457453db53366ebf35c02a6dda661a1b94060f", "created_at": "2026-11-01T15:41:08Z", "updated_at": "2026-11-01T21:23:41Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Target Analysis and Mechanism of Podophyllotoxin in the Treatment of Triple-Negative Breast Cancer.", "doi": "10.3389/fphar.2020.01211", "pmid": "32848800", "authors": ["Wenfeng Zhang", "Cun Liu", "Jie Li", "Ruijuan Liu", "Jing Zhuang", "Fubin Feng", "Yan Yao", "Changgang Sun"], "journal": "Frontiers in pharmacology", "year": 2020, "abstract": "BACKGROUND: As the original compound of many podophyllotoxin derivatives, podophyllotoxin has a beneficial antitumor effect. The mechanism of podophyllotoxin activity in triple-negative breast cancer still needs to be explored.\nMETHODS: We used cell proliferation assay, scratch and transwell experiments, and cell cycle and apoptosis analyses to observe the intervention effect of podophyllotoxin on breast cancer. Furthermore, we analyzed the differences between GSE31448, GSE65194, and GSE45827 in the Gene Expression Omnibus database (GEO) and explored the differential genes using a STRING database. Centiscape2.2, MCODE cluster analysis and KEGG pathway analysis were used to identify the most significant gene differences. Next, we utilized BATMAN-TCM and TCMSP databases for further screening to identify key genes. Finally, quantitative RT-PCR (qRT-PCR) and Western blotting were performed to detect the expression of key targets.\nRESULTS: Our research confirmed that podophyllotoxin could not only inhibit the migration and invasion of triple-negative breast cancer but also affect the cell cycle and induce apoptosis. In total, 566 differential genes were obtained by using the GEO database. After topological network analysis, cluster analysis, and molecular docking screening, we finally identified PLK1, CCDC20, and CDK1 as key target genes. The results of the qRT-PCR assay showed that the mRNA levels of PLK1, CDC20, and CDK1 decreased, while the expression of upstream P53 increased, after drug induction. The Gene Set Enrichment Analysis (GSEA) and conetwork analysis showed that PLK1 is a more critical regulatory factor. Further Western blotting analysis revealed that there was a negative regulatory relationship between the key gene PLK1 and P53 on the protein level. The results were presented as the mean ± standard deviation of triplicate experiments and P<0.05 was considered to indicate a statistically significant difference.\nCONCLUSION: Podophyllotoxin has an intervention effect on the development of triple-negative breast cancer. The expression of PLK1, CDC20, and CDK1 in the cell cycle pathway is inhibited by regulating P53. Our research shows that natural drugs inhibit tumor activity by regulating the expression of cyclins, and the combination of natural drugs and modern extensive database analysis has a wide range of potential applications in the development of antitumor therapies.", "claims": [{"id": "claim-method", "statement": "For continuous data obtained from in vitro experiments, significant differences were determined using the Student’s t-test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32848800", "locator": "sections[14] \"Statistical Analysis\" paragraph 2", "quote": "For continuous data obtained from in vitro experiments, significant differences were determined using the Student’s t-test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: GSE65194, GSE45827, GSE31448. The data can be found in https://www.ncbi.nlm.nih.gov/geo/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32848800", "locator": "sections[26] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: GSE65194, GSE45827, GSE31448. The data can be found in https://www.ncbi.nlm.nih.gov/geo/."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:32848800"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE31448"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE31448"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32848800", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fphar.2020.01211", "sha256": "sha256:50d637411a70036ed29418560368c2c368111c0417cbe396b36c04d55ffb3efa", "bytes": 43055, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fphar.2020.01211", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7427588", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE31448", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31448", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE31448", "version": null, "note": "Publicly available datasets were analyzed in this study. 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