Propofol-Induced Metabolic, Apoptotic, and Wnt–Frizzled-Related Transcript Changes in MIA PaCa-2 Cells: In Vitro and Bioinformatic Analyses

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–Frizzled-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 0–20 µM, and apoptosis was evaluated via Annexin V-FITC/7-AAD flow cytometry at the MTT-derived IC50 concentration of 7.6 µM. Transcript abundance of 18 pathway-associated genes was analysed via RT-qPCR following exposure to 7.6 µM 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–Hochberg 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 µM. At this concentration, total apoptosis increased from 0.67 ± 0.11% in vehicle-treated cells to 17.04 ± 2.40% following propofol exposure (p < 0.001), whereas necrosis remained minimal. The viable-cell fraction decreased from 99.30 ± 1.057% to 82.80 ± 0.841% (p < 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–Hochberg 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–Frizzled-related transcript changes in MIA PaCa-2 cells. These transcript-level observations do not establish direct functional modulation of Wnt–Frizzled 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.