Effects of polarized macrophages regulated by stefin B on proliferation, migration, invasion and epithelial-mesenchymal transition of hepatoma carcinoma cells / 西安交通大学学报(医学版)

ABSTRACT

Objective To investigate the effects of polarized macrophages regulated by stefin B (CSTB) on proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of hepatoma carcinoma cells. Methods Human monocyte THP-1 was induced to differentiate into macrophages (M0), classically activated macrophages (M1), alternatively activated macrophages (M2) and tumor associated macrophages (TAM), respectively. The recombinant lentiviral vectors containing human CSTB gene and a control lentivirus (LV-CSTB and LV-NULL, respectively) were constructed. M0, M1, M2 and TAM were transfected by LV-CSTB and LV-NULL, respectively. The IL-10 and IL-12 secretion of macrophages was detected by ELISA. MHCC97H cells were incubated with conditioned medium of macrophages transfected by LV-CSTB and LV-NULL, respectively. Proliferation, migration and invasion of MHCC97H cells were determined using Cell-Counting Kit-8 (CCK-8), wound healing and Transwell assay, respectively. The mRNA and protein expressions of E-cadherin, N-cadherin, β-catenin and Twist were assessed by quantitative RT-PCR and Western blotting, respectively. Results The IL-10 secretion of M0, M2, TAM and IL-12 of M1 transfected with LV-CSTB was significantly increased. Proliferation, migration and invasion of MHCC97H cells were significantly raised by the conditioned medium of M0, M2 and TAM transfected with LV-CSTB. The conditioned medium of M0, M2 and TAM also promoted mRNA and protein expressions of N-cadherin, β-catenin (except for M0) and Twist in MHCC97H cells, while the expression of E-cadherin was downregulated. Conclusion CSTB can regulate the macrophages' polarization from M0 to M2, thus promoting the proliferation, migration, invasion and epithelial-mesenchymal transition of hepatoma carcinoma cells.