{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:27:20Z","timestamp":1791822440923,"version":"4.3.4"},"reference-count":47,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Pancreatic cancer (PaCa) has an extremely poor prognosis. This malignancy rapidly acquires resistance to gemcitabine (GEM), a key chemotherapeutic agent, yet the mechanisms underlying this resistance remain incompletely understood. We previously established GEM-resistant (GEM-R) PaCa cell lines and found that these cells exhibit constitutively increased levels of matrix metalloproteinase-1 (MMP-1), which contributes to the invasion and metastasis of PaCa. Kaempferol, a naturally occurring flavonoid found in many plant species, has been shown to exhibit antitumor effects across a range of cancers. Methods\/Results: This study demonstrated that non-cytotoxic concentrations of kaempferol significantly decrease MMP-1 protein expression in GEM-R PaCa and suppress their migration and invasion capacities. Western blot analysis demonstrated that MMP-1 protein levels were upregulated in GEM-R PaCa cells and decreased upon kaempferol exposure. In Transwell migration\/invasion and wound healing assays, GEM-R PaCa cell lines exhibited enhanced migration and invasion capacities compared with GEM-S cells, whereas kaempferol treatment suppressed these properties, similar to the effects observed by MMP-1 knockdown or treatment with the MMP inhibitor batimastat. Furthermore, kaempferol treatment reduced phosphorylated Akt expression and NF-\u03baB p65 activity. Conclusions: These findings indicate that kaempferol suppresses the migratory and invasive abilities of PaCa cells by downregulating MMP-1 through negative regulation of the Akt and NF-\u03baB signaling cascades, while kaempferol holds promise as a treatment strategy for GEM-R PaCa.<\/jats:p>","DOI":"10.3390\/nu18030380","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T17:52:38Z","timestamp":1769190758000},"page":"380","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Kaempferol Inhibits MMP-1-Mediated Migration and Invasion in Gemcitabine-Resistant Pancreatic Cancer Cells"],"prefix":"10.3390","volume":"18","author":[{"given":"Saburo","family":"Sugita","sequence":"first","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9654-6080","authenticated-orcid":false,"given":"Yoichi","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, East Medical Center, Graduate School of Medical Sciences, Nagoya City University, Nagoya 464-8547, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuriko","family":"Uehara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Eguchi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Denda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Nonoyama","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromichi","family":"Murase","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomokatsu","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenta","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushi","family":"Yamakawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Sagawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Graduate 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