We further detected the expressions of invasive and metastasis-associated genes (PTEN, MMP2, and MMP9) in HCC cells grown on 6- and 16-kPa stiffness substrates in the presence or absence of metformin intervention and found that metformin intervention could remarkably upregulate the expression of PTEN and downregulate the expressions of MMP2 and MMP9 in HCC cells irrespective of being grown on a 16- or 6-kPa stiffness substrate. Here, MMP9 is linked to hepatocellular carcinoma.