Study on the role and mechanisms of sevoflurane in promoting macrophage M2 polarization in malignant progression of esophageal cancer through activation of IL-6/HO-1 pathway
LI Fei
WANG Junhui
HUANG Yanan
WANG Rong
LI Yanlei
Abstract：Objective To investigate the role of sevoflurane(SEV)in regulating and inducing macrophage M2 polarization on the malignant progression of esophageal cancer and its possible mechanism.Methods Mononuclear THP-1 cells were induced to differentiate into M0 macrophages(M φ)using phorbol myristic acid acetate(100 nmol/L).The experiments were divided into control group,M φ group,M φ+SEV group,M φ+overexpression control(oe-NC)group,M φ+heme oxygenase-1(HO-1)overexpression(oe-HO-1)group,M φ+knockdown control(sh-NC)group,M φ+HO-1 knockdown(sh-HO-1)group,M φ+SEV+sh-HO-1 group,M φ+oe-interleukin-6(IL-6)group,M φ+oe-IL-6+sh-NC group,and M φ+oe-IL-6+sh-HO-1 group.KYSE180 human esophageal cancer cells were cultured separately in macrophages conditioned medium from each group.qRT-PCR and Western blot were used to detect the mRNA and protein expression of IL-6,HO-1,and macrophage polarization related genes,while Transwell assay was used to detect cancer cell migration and invasion.Results In macrophages,Arg1,YM1,IL-4,IL-6 and HO-1 expression was elevated and iNOS expression was decreased in the Mφ+SEV group compared to the Mφ group;Arg1,YM1 and IL-4 expression was increased and iNOS expression was decreased in the Mφ+oe-HO-1 group compared to the Mφ+oe-NC group;compared to the Mφ+sh-NC group,Mφ+sh-HO-1 group had decreased Arg1,YM1 and IL-4 expression and elevated iNOS expression;compared with the Mφ+SEV group,the Mφ+SEV+sh-HO-1 group had decreased Arg1,YM1 and IL-4 expression and elevated iNOS expression.Analysis of the Starbase website showed that there was a co-expression relationship between IL-6 and HO-1 in esophageal cancer tissue samples from TCGA database.Compared with the Mφ+oe-NC group,IL-6 and HO-1 expression was elevated in the Mφ+oe-IL-6 group;compared with the Mφ+oe-NC group,IL-6,HO-1,Arg1,YM1,and IL-4 expression was elevated in the Mφ+oe-IL-6 group,and iNOS expression was decreased;and compared with the Mφ+sh-NC group,IL-6,HO-1,Arg1,YM1,and IL-4 expression was decreased in the Mφ+sh-IL-6 group,and iNOS expression was elevated;compared with Mφ+SEV group,IL-6,HO-1,Arg1,YM1 and IL-4 expression was decreased and iNOS expression was elevated in Mφ+SEV+sh-IL-6 group(P＜0.05).In KUSE180 cells,the number of migrating and invading cells was elevated in the Mφ and Mφ+SEV groups compared to the Control group;the number of migrating and invading cells was higher in the Mφ+SEV group compared to the Mφgroup;the number of migrating and invading cells was elevated in the Mφ+oe-HO-1 group compared to the Mφ+oe-NC group;the number of migrating and invading cells was decreased in the Mφ+sh-HO-1 group compared to the Mφ+sh-NC group;the number of migrating and invading cells was decreased in the Mφ+SEV+sh-HO-1 group compared to the Mφ+SEV group;the number of migrating and invading cells was increased in the Mφ+oe-IL-6 group compared to the Mφ+oe-NC group;the number of migrating and invading cells decreased in the Mφ+oe-IL-6+sh-HO-1 group compared with the Mφ+oe-IL-6+sh-NC group(P＜0.05).The differences were statistically significant.Conclusions SEV may promote macrophage M2 polarization by activating the IL-6/HO-1 pathway,and accelerate esophageal cancer cell migration and invasion.
Keywords：SevofluraneIL-6/HO-1 pathwayMacrophageMigrationInvasion
Publication Date：2025-10-20
Online Publishing Date：2025-11-06(First online date of this platform, not the publication date of the document)
Pages：8( 472-479 )