Effects of Two Concentrations of a Clinical Propofol Formulation on Canine Mammary Tumor Cells NET1 Gene Expression: A Preliminary Evaluation of Possible Anti-Metastatic Properties

Background: Several studies show that anesthesia for primary cancer surgery might influence cancer recurrence regulating specific gene expression like the Neuroepithelial transforming (NET) 1 protein. This gene has been associated with malignant behaviors and represents a novel prognostic marker in human epithelial cancers. The present study investigates the in vitro effects of a clinically available propofol formulation on NET1 expression in canine mammary tumor cells, as a potential translational model. Methods: Two canine mammary tumor cell lines, primary (CIPp) and metastatic (CIPm), were incubated with propofol (1-10 μg ml-1). Cells were lysate and RNA isolated at pre-established time points. A quantitative PCR was performed to evaluate NET1 gene expression and resulting delta cycle thresholds compared. Results: Baseline NET1 gene expression was lower in CIPm compared with CIPp. Both propofol concentrations increased NET1 mRNA levels in CIPp after 6 hours. In CIPm the higher propofol concentration caused a reduction in gene expression after 6 hours. Propofol decreased gene expression in both cell lines and only in CIPp after 12 and 24 hours, respectively. No differences were found in CIPm after 48 hours. The higher concentration of propofol increased gene expression in CIPp after 48 hours. Conclusions: Metastatic cells showed a lower basal NET1 expression and were less responsive to treatments compared to primary tumor cells. Propofol effectively influenced NET1 gene expression without a clear dose dependency. Most treatment time-points showed a decreased NET1 gene expression, although increases were also observed. Keywords: Anesthesia cancer; canine mammary tumor; NET1 gene; propofol.Peer reviewe