The migration ability of NCM460 cells increased significantly (p < 0.05) after cultivation in HT29 cell medium (high glucose), while LF suppressed the progression of T2D to colon cancer by regulating the 5′-nucleotidase domain-containing 3 (NT5DC3) protein and the PI3K/AKT/mTOR signaling pathway in diabetic BALB/c mice and in cell models. The gene discussed is NT5DC3; the disease is malignant colon neoplasm.