Abstract

Cervical cancer is a prevalent gynecological malignancy, and surgical resection can be curative for early-stage disease. Propofol is a commonly used intravenous anesthetic during cervical cancer surgery. However, the effects of propofol on the biological behavior, mRNA transcription, and lipid metabolism of cervical cancer cells remain unclear. In this study, we investigated the impact of clinical-relevant concentrations of propofol on the migration, invasion, transcriptional profiles, and lipid metabolomics of HeLa and C-33 A cells in vitro. HeLa and C-33 A cells were treated with 10 µg/ml propofol or propofol injectable emulsion (PIE). Migration and invasion were assessed using Transwell assays. RNA sequencing (RNA-seq) and liquid chromatography electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS) were used to analyze mRNA and lipid changes. Western blot was applied to detect enzymes regulating cholesterol metabolism. The key enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) was targeted using siRNA to evaluate cholesterol metabolism. Propofol inhibited the migration of HeLa cells with 0.23-fold compared to control, while PIE restored their migratory capacity. Similarly, propofol reduced the migration of C-33 A cells to 0.22-fold of the control level, whereas PIE restored their migratory ability. RNA-seq, lipid metabolomics and western blot analysis revealed dysregulation of cholesterol metabolism by both propofol and PIE. Specifically, cholesteryl ester and triacylglycerol levels in HeLa and C-33 A cells were altered by propofol treatment, the changes can vary from several folds to hundreds of folds. Propofol modulates cholesterol metabolism in cervical cancer cells, which may impact their migratory potential.