The systemic treatment of SIS3 significantly inhibited the phosphorylation of Smad3 in both LLC and B16F10 tumour tissues and suppressed cancer progression in a dosage-dependent manner, resulting in a 100% survival rate (Figs 6a–d and 7a and Supplementary Figs 11A–D and 12A). This evidence concerns the gene SMAD3 and cancer.