[Tumor-associated macrophages promote the proliferation and migration as well as invasion of sorafenib-resistant hepatocellular carcinoma cells].

ABSTRACT

Objective To investigate the roles of tumor-associated macrophages (TAMs) and epithelial growth factor receptor (EGFR)/ß-catenin signaling pathway in sorafenib resistance of hepatocellular carcinoma cells. Methods Macrophages were isolated from peripheral blood mononuclear cells (PBMCs) and cultured in the presence of colony-stimulating factor (M-CSF) to obtain TAMs. Phenotypes of TAMs were identified. The level of epithelial growth factor (EGF) secreted by TAMs was detected by ELISA. CCK-8 assay was performed to verify the effects of EGF on HepG2 and SMMC7721 cell proliferation. TranswellTM assay was used to examine the effects of EGF on the invasion and migration ability of HepG2 and SMMC7721 cells. TAMs and hepatocellular carcinoma cells were co-cultured to study the downstream signaling pathways. Sorafenib-resistant HepG2 and SMMC7721 strains (R-HepG2 and R-SMMC7721 cells) were prepared and then subjected to Western blotting and immunohistochemistry to examine the expression levels of ß-catenin and EGFR. Results TAMs we prepared were confirmed. Compared with HepG2 and SMMC7721 cells, R-HepG2 and R-SMMC7721 showed enhanced proliferation, invasion and migration abilities. The growth rates of sorafenib-resistant cell lines after co-cultured with TAMs were significantly higher than those of the controls. The protein expressions of ß-catenin and EGFR in sorafenib-resistant cells and hepatocellular carcinoma tissues were higher than those in the controls. Conclusion TAMs and EGFR/ß-catenin signaling pathway promote the proliferation, invasion and migration of sorafenib resistance of hepatocellular carcinoma cells.