Figure 7.

Sorafenib and Regorafenib inhibit lung metastasis of osteosarcoma by inducing PINK1 expression to degrade Rab22a‐NeoF1 fusion protein. a,d) 143B and U2OS/MTX300 cells stably expressing a) Rab22a‐NeoF1‐SFB, as well as d) ZOS and ZOS‐M cells were treated with Sorafenib (5 × 10⁻⁶ m) or Regorafenib (5 × 10⁻⁶ m) for 12 h as indicated, and cell lysates were subjected to western blotting. The experiments were repeated three times independently with similar results. b,c,e,f) Quantification analyses of migration and invasion assays using the indicated cells. The depicted results are the averages of at least three independent experiments. The data are presented as the mean ± SD. A two‐sided unpaired student's t‐test was performed, and p values are shown. g) ZOS cells were treated with Sorafenib (5 × 10⁻⁶ m) or Regorafenib (5 × 10⁻⁶ m) for 12 h then lysed and immunoprecipitated using anti‐hRAD5‐8‐V1‐R5 followed by western blot analysis. The experiments were repeated three times independently with similar results. h,i) The orthotropic osteosarcoma metastasis model in vivo using ZOS‐M cells under treatment of control, Sorafenib (5 × 10⁻⁶ m), or Regorafenib (5 × 10⁻⁶ m) (n = 6 biologically independent animals). h) Representative images of mice. i) Quantification analyses of lung metastases in mice.