{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:05:17Z","timestamp":1784041517671,"version":"3.55.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive tumor of the digestive system with a very low five-year survival rate. The limited efficacy and significant toxicity of existing chemotherapy regimens make the development of novel natural therapeutic agents an urgent priority. Lycopene is a natural carotenoid that has been shown to inhibit multiple cancers. However, research specifically targeting PDAC remains relatively scarce.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study first employed bibliometric analysis to examine the research landscape and emerging trends in lycopene-related cancer research from 2016 to 2026. Subsequently, network pharmacology methods are applied to screen potential lycopene targets and PDAC-related targets from databases such as CTD, ChEMBL and HERB. Following the identification of overlapping targets, drug-target and protein\u2013protein interaction (PPI) networks are constructed, as well as a disease network. The mechanisms were explored using Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Molecular docking was used to predict the potential interactions between lycopene and representative hub targets, and molecular dynamics simulations were performed for selected high-ranking docking complexes to provide supportive information on complex-level conformational stability.\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments were then conducted to evaluate the predicted anti-PDAC effects and to perform focused validation of apoptosis-related proteins and the PI3K\/Akt\/P53 signaling axis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Publications on lycopene research in the field of cancer have shown a sustained upward trend. The focus of this research has gradually shifted from areas such as oxidative stress and antioxidant effects towards anti-cancer mechanisms. A total of 132 overlapping targets for lycopene\u2019s anti-PDAC activity were screened, leading to the identification of 10 core targets, including BCL2, AKT1, and TP53. GO enrichment analysis revealed that these targets are involved in biological processes such as the response to oxidative stress and cellular senescence. Meanwhile, KEGG enrichment analysis identified the PI3K-Akt signaling pathway as a key pathway. Molecular docking results showed that the binding energies of lycopene with core targets such as TP53 and BCL2 were below \u22124.5\u202fkcal\/mol. Molecular dynamics simulations provided supportive evidence for the conformational stability of representative lycopene-target complexes.\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments showed that lycopene inhibited the proliferation and migration of PDAC cells and promoted apoptosis-associated cell death, accompanied by decreased p-PI3K and p-AKT expression and increased P53 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study systematically combined bibliometrics, network pharmacology, molecular docking, representative molecular dynamics simulations, and focused experimental validation to explore the potential anti-PDAC activity of lycopene. The inflammation-related hub targets identified by network analysis provide additional hypotheses for future experimental investigation. These findings provide preliminary mechanistic evidence for further preclinical investigation of lycopene in PDAC, but its translational application will require optimized formulations, pharmacokinetic validation, and\n                      <jats:italic>in vivo<\/jats:italic>\n                      efficacy studies to overcome its limited bioavailability.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1815515","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T14:31:59Z","timestamp":1784039519000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating network pharmacology, molecular docking, and experimental validation to investigate the therapeutic effects and potential mechanisms of lycopene against pancreatic ductal adenocarcinoma"],"prefix":"10.3389","volume":"13","author":[{"given":"Shaoyang","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dali University","place":["Dali, Yunnan, China"]},{"name":"Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from Western Yunnan, College of Pharmacy, Dali University","place":["Dali, Yunnan, China"]},{"name":"Department of Cell Biology, College of Life Sciences, Shaanxi Normal University","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Northeast Yunnan Regional Central Hospital","place":["Zhaotong, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dali University","place":["Dali, Yunnan, China"]},{"name":"Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from Western Yunnan, College of Pharmacy, Dali University","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jintao","family":"He","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dali University","place":["Dali, Yunnan, China"]},{"name":"Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from Western Yunnan, College of Pharmacy, Dali University","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunpeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Dali University","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengliang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of Dali University","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dali University","place":["Dali, Yunnan, China"]},{"name":"Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from Western Yunnan, College of Pharmacy, Dali University","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"4125","DOI":"10.1097\/JS9.0000000000004008","article-title":"Postoperative survival prediction in 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