Objective To investigate the effects of sevoflurane (SEV) on the proliferation, migration and iron death of gastric cancer cells, and preliminarily explore the possible mechanisms.

Methods HGC-27 cells in logarithmic growth phase were selected, and divided into the control group, 1.7% SEV group (treated with 1.7% SEV), 3.4% SEV group (treated with 3.4% SEV), 5.1% SEV group (treated with 5.1% SEV) and 5.1% SEV + Fer-1 group (treated with 5.1% SEV and 1 μmol/ L iron death inhibitor Ferrostatin-1). The cell viability was detected by MTT assay. Clonal formation assay was used to detect cell proliferation. Cell migration and invasion were detected by cell scratch assay and Transwell. The cell apoptosis was detected by flow cytometry. The iron content, and reactive oxygen species (ROS) and malondialdehyde (MDA) levels were detected by corresponding kits. The mRNA expression of lipid peroxidase phospholipid glutathione peroxidase 4 (GPX4) was detected by qRT-PCR. The expression levels of GPX4, nuclear factor E2 associated factor 2 (Nrf2), heme oxygenase-1 (HO-1) and cystine/glutamate antitransporter (xCT) were detected by Western blot.

Results Compared with the Control group, the cell OD value, cell clone formation rate, cell migration distance, number of cell invasion, GPX4 mRNA and protein expression levels, and Nrf2, HO-1 and xCT protein expression levels in the 1.7% SEV, 3.4% SEV and 5.1% SEV groups decreased, which in the 3.4% SEV and 5.1% SEV groups were lower than those in 1.7% SEV group, while which in the 5.1% SEV group were lower than those in 3.4% SEV group (P ＜ 0.01). Compared with the control group, the apoptosis rate, iron content, ROS and MDA levels in the 1.7%SEV, 3.4%SEV and 5.1%SEV groups increased (P ＜ 0.01), and which in the 3.4%SEV and 5.1%SEV groups were higher than those in 1.7%SEV group (P ＜ 0.05), whereas which in the 5.1%SEV group were higher than those in 3.4%SEV group (P ＜ 0.01). Compared with the 5.1% SEV group, the cell OD value, cell clone formation rate, cell migration distance, number of cell invasion, GPX4 mRNA and protein expression, and protein expression levels of Nrf2, HO-1 and xCT increased, and the apoptosis rate, iron content and levels of ROS and MDA significantly decreased in the 5.1% SEV + Fer-1 group (P ＜ 0.05 ~ P ＜ 0.01).

Conclusions SEV can inhibit the proliferation, migration and invasion of gastric cancer cells, and promote iron death, which may be achieved by inhibiting the activation of Nrf2/xCT pathway, but the relevant mechanism remains to be further explored.