{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:15:16Z","timestamp":1790968516145,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Erciyes University Scientific Research Projects Unit","award":["TDK-2018-8652"],"award-info":[{"award-number":["TDK-2018-8652"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study aimed to evaluate the effects of dextromethorphan (DX), alone and in combination with gemcitabine (GEM), on cell viability, apoptosis, and epithelial\u2013mesenchymal transition (EMT) markers in PANC-1 human pancreatic cancer cells. PANC-1 human pancreatic cancer cells were cultured and treated with varying concentrations of dextromethorphan (DX), gemcitabine (GEM), and 5-fluorouracil (5-FU), both as monotherapies and in combination. Cytotoxic effects were assessed using the MTT assay, and IC50 values were calculated at 24, 48, and 72 h. Apoptotic responses were evaluated using Annexin V-FITC\/PI staining followed by flow cytometry. Protein expression levels of Bax, Bcl-2, and Vimentin were determined via immunocytochemistry, while EMT markers (E-cadherin, N-cadherin, Vimentin) were analyzed using flow cytometry. Relative mRNA expression of apoptotic and EMT-related genes was quantified by qRT-PCR. DX exhibited time- and dose-dependent cytotoxicity in PANC-1 cells, with IC50 values of 280.4 \u00b5M at 24 h, 163.2 \u00b5M at 48 h, and 105.6 \u00b5M at 72 h. For GEM, the 72 h IC50 was 57.53 \u00b5M. The combination of DX 50 \u00b5M + GEM 12.5 \u00b5M resulted in significantly lower cell viability (24.93 \u00b1 3.12%) compared to GEM 25 \u00b5M (35.33 \u00b1 5.22%) and DX 100 \u00b5M (51.40 \u00b1 3.10%) (p &lt; 0.001). Flow cytometry revealed significant increases in early (21.83 \u00b1 1.32%) and late apoptotic cells (32.20 \u00b1 0.84%) in the combination group, with a corresponding reduction in viable cells compared to control (24.93 \u00b1 3.12% vs. 89.53 \u00b1 0.97%, p &lt; 0.001). Immunocytochemical analysis showed increased Bax-positive cell count (62.0 cells\/unit area), and decreased Bcl-2 (19.0) and Vimentin (28.0) levels in the combination group compared to control (Bax: 15.0, Bcl-2: 60.0, Vimentin: 70.0) (p &lt; 0.001). Flow cytometry for EMT markers demonstrated increased E-cadherin (83.84 \u00b1 0.65%) and decreased Vimentin (71.04 \u00b1 1.17%) and N-cadherin (30.47 \u00b1 0.72%) expression in the DX + GEM group compared to EMT control (E-cadherin: 68.97 \u00b1 1.43%, Vimentin: 91.00 \u00b1 0.75%, N-cadherin: 62.47 \u00b1 1.13%) (p &lt; 0.001). qRT-PCR supported these findings with increased Bax (2.1-fold), E-cadherin (2.0-fold), and reduced Bcl-2 (0.3-fold) and XIAP (0.6-fold) in the combination group (p &lt; 0.05). Dextromethorphan, particularly in combination with gemcitabine, appears to enhance apoptosis and suppress EMT-associated marker expression in PANC-1 cells, supporting its potential as an adjuvant agent in pancreatic cancer therapy.<\/jats:p>","DOI":"10.3390\/ijms26178151","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T12:31:26Z","timestamp":1755865886000},"page":"8151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dextromethorphan Enhances Apoptosis and Suppresses EMT in PANC-1 Pancreatic Cancer Cells: Synergistic Effects with Gemcitabine"],"prefix":"10.3390","volume":"26","author":[{"given":"Gulsah","family":"Medet","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Institute of Health Sciences, Erciyes University, Kayseri 38039, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5917-3729","authenticated-orcid":false,"given":"Ahmet","family":"Inal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Erciyes University, Kayseri 38039, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14740\/wjon1166","article-title":"Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors","volume":"10","author":"Rawla","year":"2019","journal-title":"World J. 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