{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:02:06Z","timestamp":1789646526392,"version":"4.0.0"},"reference-count":27,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy, and there is continuing interest in whether agents used during the perioperative period influence tumour-cell biology. Propofol has been associated with antiproliferative and pro-apoptotic effects in experimental cancer models; however, its relationship with Wnt\u2013Frizzled-related transcriptional responses in pancreatic cancer cells remains incompletely characterised. MIA PaCa-2 cells were exposed to propofol for 24 h. Cellular metabolic activity was assessed using the MTT assay over a concentration range of 0\u201320 \u00b5M, and apoptosis was evaluated via Annexin V-FITC\/7-AAD flow cytometry at the MTT-derived IC50 concentration of 7.6 \u00b5M. Transcript abundance of 18 pathway-associated genes was analysed via RT-qPCR following exposure to 7.6 \u00b5M propofol. MTT, flow-cytometry, and RT-qPCR assays were each performed in three independent biological experiments (n = 3). RT-qPCR results were evaluated after Benjamini\u2013Hochberg false discovery rate correction across the 18-transcript panel. Complementary bioinformatic analyses were performed solely to provide exploratory biological and clinical context for the experimentally prioritised transcripts. Propofol produced a concentration-dependent reduction in normalised MTT metabolic activity, with an MTT-derived IC50 of 7.6 \u00b5M. At this concentration, total apoptosis increased from 0.67 \u00b1 0.11% in vehicle-treated cells to 17.04 \u00b1 2.40% following propofol exposure (p &lt; 0.001), whereas necrosis remained minimal. The viable-cell fraction decreased from 99.30 \u00b1 1.057% to 82.80 \u00b1 0.841% (p &lt; 0.05). The difference between the MTT-derived IC50 and the Annexin V\/7-AAD viable-cell fraction indicates that the MTT-derived IC50 reflects reduced metabolic activity rather than 50% cell lethality. RT-qPCR showed decreased WNT5B, FZD5, and WNT11 transcript abundance and increased GSK3B transcript abundance. All four remained significant after Benjamini\u2013Hochberg correction (WNT5B, q = 0.001; FZD5, q = 0.001; WNT11, q = 0.027; GSK3B, q = 0.041). Exploratory bioinformatic analyses showed heterogeneous gene-specific expression, survival, genomic, immune-infiltration, and dependency patterns and were not interpreted as evidence of a propofol-mediated mechanism in patients. Under the tested in vitro conditions, propofol reduced MTT-derived metabolic activity, increased apoptosis, and was associated with selective Wnt\u2013Frizzled-related transcript changes in MIA PaCa-2 cells. These transcript-level observations do not establish direct functional modulation of Wnt\u2013Frizzled signalling or demonstrate that this pathway mediates the observed apoptotic response. The bioinformatic findings provide exploratory contextual information only. Further validation in additional PDAC and non-malignant pancreatic cell models, together with protein-, phosphorylation-, and pathway-level functional studies, is required.<\/jats:p>","DOI":"10.3390\/cimb48090950","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:59:03Z","timestamp":1789639143000},"page":"950","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Propofol-Induced Metabolic, Apoptotic, and Wnt\u2013Frizzled-Related Transcript Changes in MIA PaCa-2 Cells: In Vitro and Bioinformatic Analyses"],"prefix":"10.3390","volume":"48","author":[{"given":"Irmak Fato\u015f","family":"Korkmaz","sequence":"first","affiliation":[{"name":"Department of Anaesthesia, Bah\u00e7elievler State Hospital, University of Health Science, Istanbul 34668, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1311-6892","authenticated-orcid":false,"given":"Tugba","family":"Elgun","sequence":"additional","affiliation":[{"name":"Medical Biology, Faculty of Medicine, Biruni University, Istanbul 34015, T\u00fcrkiye"},{"name":"Biruni Advanced Technology Application and Research Center (BAMER), Biruni University,  Istanbul 34015, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1448-2739","authenticated-orcid":false,"given":"\u00c7i\u011fdem","family":"Aktas","sequence":"additional","affiliation":[{"name":"Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul 34452, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajjad","family":"Eslamkhah","sequence":"additional","affiliation":[{"name":"Biruni Advanced Technology Application and Research Center (BAMER), Biruni University,  Istanbul 34015, T\u00fcrkiye"},{"name":"Program of Pathology Laboratory Techniques, Vocational School, Biruni University, Istanbul 34015, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevgi Kocyigit","family":"Sevinc","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, K\u00fctahya Health Sciences University, Kutahya 43100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6424-7411","authenticated-orcid":false,"given":"Asiye Gok","family":"Yurttas","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Istanbul Atlas University, Istanbul 34403, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","first-page":"17","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Fan, M., Deng, G., Ma, Y., Si, H., Wang, Z., and Dai, G. (2024). Survival outcome of different treatment sequences in patients with locally advanced and metastatic pancreatic cancer. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-11823-8"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Serafini, S., Sperti, C., Friziero, A., Brazzale, A.R., Buratin, A., Ponzoni, A., and Moletta, L. (2021). Systematic review and meta-analysis of surgical treatment for isolated local recurrence of pancreatic cancer. Cancers, 13.","DOI":"10.3390\/cancers13061277"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Lai, H.C., Kuo, Y.W., Huang, Y.H., Chan, S.M., Cheng, K.I., and Wu, Z.F. (2022). Pancreatic cancer and microenvironments: Implications of anesthesia. Cancers, 14.","DOI":"10.3390\/cancers14112684"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"52","DOI":"10.3892\/mmr.2020.11690","article-title":"Regulation of ABCG2 expression by Wnt5a through FZD7 in human pancreatic cancer cells","volume":"23","author":"Zhang","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Gu, L., Pan, X., Wang, C., and Wang, L. (2022). The benefits of propofol on cancer treatment: Decipher its modulation code to immunocytes. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.919636"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/jhbp.624","article-title":"Propofol inhibits pancreatic cancer progress under hypoxia via ADAM8","volume":"26","author":"Gao","year":"2019","journal-title":"J. Hepato-Biliary-Pancreat. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103749","DOI":"10.1016\/j.critrevonc.2022.103749","article-title":"Prospects of targeting PI3K\/AKT\/mTOR pathway in pancreatic cancer","volume":"176","author":"Mortazavi","year":"2022","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.ejphar.2018.04.009","article-title":"Effects of propofol on cancer development and chemotherapy: Potential mechanisms","volume":"831","author":"Jiang","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Aguilera, K.Y., and Dawson, D.W. (2021). WNT ligand dependencies in pancreatic cancer. Front. Cell. Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.671022"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/nrc2899","article-title":"KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma","volume":"10","author":"Morris","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_12","first-page":"402","article-title":"Propofol inhibits Wnt signaling and exerts anticancer activity in glioma cells","volume":"16","author":"Xu","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1042\/bj2960015","article-title":"Inactivation of glycogen synthase kinase-3 beta by phosphorylation: New kinase connections in insulin and growth-factor signalling","volume":"296","author":"Sutherland","year":"1993","journal-title":"Biochem. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8602","DOI":"10.1038\/s41598-017-09239-5","article-title":"In vivo regulation of glycogen synthase kinase 3\u03b2 activity in neurons and brains","volume":"7","author":"Krishnankutty","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5612","DOI":"10.1158\/1078-0432.CCR-15-0789","article-title":"Glycogen synthase kinase 3 beta predicts survival in resected adenocarcinoma of the pancreas","volume":"21","author":"George","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1186\/s13046-021-02187-z","article-title":"WNT11\/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer","volume":"40","author":"Menck","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5485","DOI":"10.3748\/wjg.v19.i33.5485","article-title":"Propofol induces apoptosis and increases gemcitabine sensitivity in pancreatic cancer cells in vitro by inhibition of nuclear factor-\u03baB activity","volume":"19","author":"Du","year":"2013","journal-title":"World. J. Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.21873\/invivo.13008","article-title":"Effect of propofol and etomidate on the proliferation, cell-cycle distribution, apoptosis and necrosis of pancreatic tumour cells","volume":"36","author":"Malsy","year":"2022","journal-title":"In Vivo"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhao, M.Y., Liu, P., Sun, C., Pei, L.J., and Huang, Y.G. (2022). Propofol augments paclitaxel-induced cervical cancer cell ferroptosis in vitro. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.816432"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e6803","DOI":"10.1590\/1414-431x20176803","article-title":"Propofol inhibits proliferation; migration, and invasion but promotes apoptosis by regulation of Sox4 in endometrial cancer cells","volume":"51","author":"Du","year":"2018","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7698706","DOI":"10.1155\/2023\/7698706","article-title":"Propofol-induced miR-493-3p inhibits growth and invasion of gastric cancer through suppression of DKK1-mediated Wnt\/\u03b2-catenin signaling activation","volume":"2023","author":"Zhan","year":"2023","journal-title":"Dis. Markers"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10771","DOI":"10.2147\/CMAR.S270344","article-title":"Propofol inhibits proliferation and invasion of stomach cancer cells by regulating miR-205\/YAP1 axis","volume":"12","author":"Xian","year":"2020","journal-title":"Cancer Manag. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1097\/ALN.0000000000000936","article-title":"Long-term survival for patients undergoing volatile versus IV anesthesia for cancer surgery: A retrospective analysis","volume":"124","author":"Wigmore","year":"2016","journal-title":"Anesthesiology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1016\/S0140-6736(19)32313-X","article-title":"Recurrence of breast cancer after regional or general anaesthesia: A randomised controlled trial","volume":"394","author":"Sessler","year":"2019","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.bja.2023.01.023","article-title":"Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: Follow-up of a multicentre randomised trial","volume":"131","author":"Cao","year":"2023","journal-title":"Br. J. Anaesth."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Chiu, W.C., Wu, Z.F., Lee, M.S., Chen, J.Y.H., Huang, Y.H., Tseng, W.C., and Lai, H.C. (2024). Propofol-based total intravenous anesthesia is associated with less postoperative recurrence than desflurane anesthesia in thyroid cancer surgery. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0296169"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s13741-024-00436-1","article-title":"Recurrence-free survival after curative resection of non-small-cell lung cancer between inhalational gas anesthesia and propofol-based total intravenous anesthesia: A multicenter, randomized, clinical trial (GAS TIVA trial): Protocol description","volume":"13","author":"Kim","year":"2024","journal-title":"Perioper. Med."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/9\/950\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:06:07Z","timestamp":1789643167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/9\/950"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":27,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cimb48090950"],"URL":"https:\/\/doi.org\/10.3390\/cimb48090950","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]}}}