Sevoflurane inhibits the migration and invasion of colorectal cancer cells through regulating ERK/MMP‐9 pathway by up‐regulating miR‐203

Abstract

ABSTRACT Surgery resection is the primary treatment for colorectal cancer (CRC) patients with the risk of cancer dissemination and metastasis. Sevoflurane is one inhalational anesthesia which regulates migration and invasion in varying cancers. However, the effect of sevoflurane on CRC cells and its mechanism remain poorly understood. In this study, SW620 and HCT116 cells were treated with different concentrations of sevoflurane for 6h in vitro. We measured the effect of sevoflurane on cell survival, migration and invasion by 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide or trans‐well assays. Moreover, we explored the interaction between sevoflurane and miR‐203 and Roundabout1 (Robo1) as well as the extracellular signal‐regulated kinase (ERK) and matrix metalloproteinase‐9 (MMP‐9) pathway. Results showed that sevoflurane inhibited cell migration and invasion in SW620 and HCT116 cells in a concentration dependent manner. Moreover, different concentrations of sevoflurane suppressed the phosphorylation of ERK. miR‐203 expression was impaired while sevoflurane reversed the expression of miR‐203 in CRC cells. In addition, inhibition of miR‐203 attenuated the inhibitory effect of sevoflurane on cell migration, invasion and phosphorylated ERK level. Notably, MMP‐9, as a downstream of ERK, was involved in sevoflurane‐mediated processes in CRC cells. Besides, Robo1 was indicated as a target of miR‐203 and inhibited by sevoflurane treatment. These results indicated that sevoflurane suppressed cell migration and invasion through regulating ERK/MMP‐9 pathway via miR‐203/Robo1 in CRC cells, indicating important clinical implications for anesthetic agents to prevent metastasis in CRC.