Abstract
Perioperative anesthesia might directly alter cancer cell biology. We investigated the effects of levobupivacaine treatment on lung adenocarcinoma cells. A549 cells were treated with levobupivacaine at concentrations of 0.1 mM and 0.5 mM for 2 h. Transfection with angiotensin-converting enzyme 2 (ACE2) small interfering RNA (siRNA) was performed 6 h before the levobupivacaine treatment. Cell proliferation was assessed using a cell counting kit 8 (CCK-8), and ATP synthesis was evaluated with the CellTiter-Glo(®) 2.0 assay at 0 and 24 h after anesthesia exposure. RT-PCR was performed to examine various biomarkers. The levobupivacaine treatment suppressed ATP synthesis without affecting cell proliferation. This was associated with the upregulation of ACE2 and the downregulation of pro-cancer biomarkers, including HIF-1α, MMP-9, and β-catenin. The anticancer effect of levobupivacaine was negated when ACE2 siRNA was introduced, and it was further suppressed when combined with levobupivacaine. The RT-PCR results indicated that the expressions of B-cell/CLL lymphoma 2 (BCL2) and wingless/integrated 1 (WNT1) were reduced after levobupivacaine treatment, but these effects were reversed with ACE2 siRNA induction. The administration of levobupivacaine suppressed A549 cell metabolism and downregulated HIF-1α, MMP-9, WNT1, EGFR, and BCL2 in an ACE2-dependent manner.