In vivo combination therapy with PKN3 siRNA and DXR in mice with liver MCF-7 metastasis. In (A-C), DXR, followed by PKN3 siRNA was administered to mice on day 8 after inoculation, and PKN3 siRNA was administered on days 10, 12, and 14. The mice were sacrificed at day 16 after inoculation, and then the excised livers were weighed. In (C), the luciferase activities in livers shown in (A and B) were measured. Luciferase activity (%) was calculated relative to the luciferase activity (cps/organ) of untreated liver. In (A-C), each result represents the mean ± standard deviation (n=4-6). In (A and B), *P<0.05, **P<0.01, compared with PKN3 siRNA and DXR. In (D), on day 15 after the inoculation, DXR, followed by PKN3 siRNA was administered to mice. DXR concentrations in livers were measured at 24 h after injection of siRNA by high-performance liquid chromatography (HPLC). Each column shows the mean ± standard deviation (n=3). In (C and D), *P<0.05, **P<0.01. N.S., not significant; PKN3, protein kinase N3; Cont, control; siRNA, small interfering RNA; DXR, doxorubicin.