The mechanism of sevoflurane affecting ovarian cancer cell proliferation and migration by regulating RNA methylase TRDMT1 to activate the β-catenin pathway.

Objective: Sevoflurane (Sevo), a commonly used inhalant anesthetic clinically, is associated with a worsened cancer prognosis, and we investigated its effect on RNA methylase tRNA aspartic acid methyltransferase 1 (TRDMT1) expression and ovarian cancer (OC) cell malignant phenotypes.
Methods: Human OC cells (OVCAR3/SKOV3) were pretreated with 3.6% Sevo and cultured under normal conditions for 48 h, with their viability assessed. After 2-h Sevo treatment or interference plasmid transfections to down-regulate TRDMT1/adenomatous polyposis coli (APC), changes in TRDMT1, APC and β-catenin expression, cell proliferative activity, cycle, apoptosis, migration, invasion, and 5-methylcytosine (m5C) methylation potential modification sites were evaluated. Additionally, APC mRNA m5C methylation level and stability, the binding of APC mRNA with TRDMT1, the binding intensity of APC and β-catenin, and β-catenin nuclear translocation were detected Lastly, Cyclin D1, cellular-myelocytomatosis viral oncogene (C-myc) and β-catenin protein levels, and ki67-positive rate were assessed.
Results: Sevo treatment boosted cell cycle, proliferation, migration and invasion, suppressed apoptosis and APC expression, and up-regulated C-myc, β-catenin, TRDMT1 and Cyclin D1 levels. Silencing TRDMT1 or β-catenin partially averted Sevo-mediated promotion effects on cell malignant biological behaviors. Lowly-expressed APC annulled the effect of silencing TRDMT1 and promoted cell malignant behaviors. Sevo enhanced APC mRNA m5C modification and degradation and activated the APC/β-catenin pathway by increasing TRDMT1, thus encouraging OC growth in vivo.
Conclusions: Sevo stimulated APC m5C modification and curbed its expression by up-regulating TRDMT1, which in turn activated the β-catenin pathway to stimulate OC cell cycle, invasion, proliferation, and migration and to suppress apoptosis.
Competing Interests: Declarations. Ethics approval: All animal experiments were approved by the ethics committee of The Third Bethune Hospital of Jilin University. Considerable efforts were conducted to minimize the animal number and their pain. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)