Abstract

Background Anesthetics might be involved in tumor progression. This study examined the role of isoflurane in the progression of colorectal cancer (CRC). Objectives To determine whether isoflurane exerted anti‑CRC effect through the PI3K/Akt/NF‑κB pathway. Methods In-vitro assays including cell counting kit-8 (CCK-8), 5-Ethynyl-2’-deoxyuridine (EdU), wound healing, Transwell, and flow cytometry were performed to analyze the potential role of isoflurane in CRC using SW620 and HCT116 cell lines. Potential molecular mechanisms of isoflurane were explored based on the levels of proteins related to metastasis (E-cadherin, N-cadherin, and Vimentin), apoptosis (Bcl-2 family proteins and Cleaved Caspase-3), and the phosphoinositide 3-kinase (PI3K)/Akt/NF‑κB signaling pathway. A rescue assay using PI3K/Akt agonist 740 Y-P was performed to further confirm the mechanisms of isoflurane in CRC cells. Results Isoflurane suppressed the viability and proliferation, reduced migration and invasion, and increased apoptosis in CRC cell lines (SW620 and HCT116, p  < 0.05). Meanwhile, isoflurane treatment increased the protein levels of E-cadherin, Bax, and Cleaved Caspase-3 and decreased those of N-cadherin, Vimentin and Bcl-2 ( p  < 0.05). Regarding the PI3K/Akt/NF‑κB pathway, isoflurane markedly suppressed the phosphorylation of PI3K, Akt, and p65 ( p  < 0.05). Mechanistically, additional treatment of isoflurane-exposed CRC cells with 740 Y-P abrogated the effects of isoflurane ( p  < 0.05). Conclusion Collectively, the current study provided preliminary evidence for the anti-CRC effects of isoflurane using a cellular model. However, animal models are required to validate the findings.