Our systematic experiments demonstrated that (i) DLD-1 and SW480 CRC cells cultured in ACM environment could upregulate the SREBP-1 expression and hence decrease their sensitivity to 5-FU cytotoxicity; (ii) Akt and p70S6K signaling pathways regulate the ACM effect on SREBP-1 upregulation and 5-FU-induced cell death in CRC cells. Here, AKT1 is linked to colorectal carcinoma.