Hypoxia microenvironment enhances MACC1 regulation of PI3K/AKT signaling pathway and promotes colon cancer stem cell like characteristics
Aim To investigate the effects and mechanism of hypoxia microenvironment and metastasis-associated colon cancer 1(MACC1)on the biological behavior of colorectal cancer(CRC)tumor stem cell(CSC)like properties.Methods Co-lon cancer cells HCT116 were transfected with empty vector(LV ctrl group)and MACC1 overexpression vector(LV-MACC1 group),and LV-MACC1 cells(LV-MACC 1+Hypoxia group)were cultured under hypoxic microenvironment conditions.CCK-8 assay and im-munocytochemistry,wound healing assay,transwell invasion experiment,and tumor sphere formation assay,were used to measure cell proliferation,migration,invasion abilities and tumor formation capacity of cancer cells,respectively.Western blotting test was used to detect expression of difference of protein level of MACC1,CD 133,CD44,AKT and p-AKT.To determine the possible roles of PI3K/AKT in MACC1-induced stem cell properties,740 Y-P was applied.Results Compared with the LV-ctrl group,the cell proliferation,migration and invasion ability of LV-MACC1 group,the formation of spheres,and the expression level of CD44,CD133 and p-AKT proteins in LV-MACC1 group,were all increased(P＜0.05).Compared with the LV-MACC1 group,the cell prolifera-tion,migration and invasion ability of LV-MACC1+hypoxia group,the formation of spheres(P＜0.05),and the expression level of CD44,CD133 and p-AKT protein,were all increased(P＜0.05).Protein expression levels of CD 133 and CD44 were increased in response of HCT116 cells to 740 Y-P,compared with in the control group(P＜0.05).Conclusion Hypoxia microenvironment enhanced the ability of MACC1 to facilitate cancer stem cell like properties and malignant biological behavior in colorectal cancer cells through the PI3K/AKT signaling pathway.
colorectal cancercancer stem cellsmetastasis-associated colon cancer 1hypoxia microenvironment
万方数据
维普
