Promotion of tumor immune escape by PI3K/Akt and MEK/ERK-mediated endothelial cells in colorectal cancer

This study aims to discuss the impact of PI3K/AKT and MEK/ERK signaling pathway on the promotion of tumor immune escape by colorectal cancer endothelial cells (CCVEC). SW480 freeze-thaw lysate is applied to load DC, to induce CTL with specific cytotoxicity of SW480. The co-culture system of SW480 human colorectal cancer cells and human umbilical vein endothelial cells HUVEC is constructed, and according to different intervening factors in the chamber above, the system can be divided into (1) SW480 and HUVEC co-culture group, (2) SW480 culture group, (3) DMSO group, (4) PI3K/AKT inhibitor LY294002 group: a final concentration of 10 nM and (5) MEK/ERK inhibitor PD98059 group: a final concentration of 20 nM. ELISA assay is used to test the influence of CTL tumor vascular endothelial cells on the secretion of IL-2 and INF-gamma, FACS is used to detect the apoptosis rate of SW480, RT-qPCR and western blot is used to detect the expressions of B7-H1, FasL, TGF-beta and COX-2 in SW480 cells. The results show colorectal cancer-associated endothelial cells can enhance the expressions of B7-H1, FasL, TGF-beta and COX-2 in SW480 cells, and reduce the secretion of tumor-specific CTL cells, IL-2 and INF-gamma and the destruction capability. Inhibiting the signals of the endothelial cells related to colorectal cancer, PI3K/AKT and MEK/ERK could reverse this phenomenon above. So it is concluded that CCVEC can promote tumor immune escape of colorectal cancer, and PI3K/AKT and MEK/ERK signals play an important role in this process.