-Original-

Midazolam and Dexmedetomidine Promoted Migration of Human Lung Adenocarcinoma A549 Cells

Anna Ishikawa, Masae Iwasaki, Masahiro Tomihari, Makiko Yamamoto and Masashi Ishikawa

Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan

Background: The numerous studies of the effects of intravenous anesthetics on cancer have suggested potential effects on cell migration and postoperative outcomes. This study compared the direct effects of midazolam and dexmedetomidine on A549 human lung adenocarcinoma cells.
Methods: A549 cells were exposed for 2 hr to midazolam (5, 10, 15, 20 μM), dexmedetomidine (1, 10, 100 nM), or medium alone as a naïve control. Cell viability changes were assessed with a wound healing assay, adenosine triphosphate (ATP) analysis, and cell counting kit-8 (CCK) assay. Tumor metastasis-related gene expression was assessed by a polymerase chain reaction (PCR) array and qRT-PCR. Hypoxia-inducible factor (HIF-1α), angiotensin-converting enzyme 2 (ACE2), matrix metalloproteinase (MMP9), and β-catenin expressions were assessed by immunofluorescence staining.
Results: Midazolam treatments promoted cell migration and metabolism but suppressed cell proliferation, whereas D treatments promoted cell migration only and had no effect on metabolism or cell proliferation. The PCR array of cancer-related genes revealed that five genes were upregulated by midazolam treatment relative to naïve controls: Frizzled-1 (FZD1), AKT serine/threonine kinase 2 (AKT2), E2F transcription factor 1 (E2F1), Fos proto-oncogene, AP-1 transcription factor subunit (FOS), and tumor protein p53 (TP53). Two genes were upregulated in the dexmedetomidine group: the CRK proto-oncogene, adaptor protein (CRK) and FZD1.
Conclusions: These findings clarify how dexmedetomidine and midazolam treatments affect lung cancer prognoses. Our data suggest that midazolam rather than dexmedetomidine should be recommended for lung cancer surgery.

J Nippon Med Sch 2026; 93: 161-172

Keywords
cancer biology, intravenous anesthetics, dexmedetomidine, midazolam, ACE2

Correspondence to
Masae Iwasaki
masae-a@nms.ac.jp

Received, August 9, 2025
Accepted, December 17, 2025