Sevoflurane Inhibits Colon Cancer Progression by Inducing Cell Autophagy and Apoptosis through the ROS/Nrf2/P62 Pathway.

Objectives

There is debate over the effect of sevoflurane (SEV) on different cancers. This study aims to explore SEV's role in colon cancer (CC) progression.

Methods

The CC cell lines were treated with SEV at concentrations of 1.7%, 3.4%, and 5.1%. Cell proliferation, apoptosis, migration, and invasion were assessed using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation, colony formation assay, flow cytometry, Western blot, scratch assay, and Transwell assay. A xenograft tumor model was established to evaluate the effect of SEV in vivo. Expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), p62 (sequestosome-1), microtubule-associated protein 1 light chain 3 isoform II to I ratio (LC3-II/I), Beclin-1, Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) were measured. N-acetyl-L-cysteine (NAC), a ROS scavenger, was applied to determine whether ROS-dependent Nrf2/p62 signaling participated in this process.

Results

SEV inhibited CC cell proliferation, colony formation, migration, and invasion. At 5.1% SEV, cell proliferation was reduced by 54.0% (p < 0.001); colony formation decreased by 55.0% (p < 0.001); and wound closure rates dropped from 78.3% to 24.6% (p < 0.001) in HCT116 cells. Similar trends were observed in SW480 cells. Invaded cells were also significantly reduced in both cell lines (p < 0.001). SEV also induced CC apoptosis. In the xenograft model, treatment with SEV significantly suppressed tumor progression, as evidenced by reductions in both tumor volume and weight (p < 0.001). Mechanistically, SEV increased the LC3-II/I ratio and Beclin-1 expression, while decreasing Nrf2 and p62 expression both in vitro and in vivo. Moreover, NAC reversed the SEV-induced effects in vitro.

Conclusion

SEV inhibits CC progression by inducing autophagy and apoptosis via the ROS/Nrf2/p62 pathway.