Fig. 8

BP-Combo represses the growth and metastasis of liver orthotopic xenografts and has no obvious toxicity on normal tissues. a, b BP-Combo suppressed the growth of liver orthotopic xenografts. Hepa1-6 cells were inoculated under the capsule of the left hepatic lobe of C57BL/6 mice. Vehicle or BP-Combo treatment was intraperitoneally administered at the indicated time. The tumor incidences and photographs of dissected livers (a) and the tumor volume (b) are shown. c, d BP-Combo suppressed metastasis of liver xenografts. The representative images of H&E staining and metastasis rates (left panel) and the number of the intrahepatic (c) or pulmonary (d) metastatic foci (right panel) are shown. Scale bar, 50 μm (c) and 25 μm (d). Met. metastases. e, f The proportion of hematopoietic stem and progenitor cells were not affected in BP-Combo-treated mice. Bone marrow cells were isolated from the vehicle or BP-Combo-treated mice and analyzed by flow cytometry to detect CD117⁺Sca1⁺ population (e) and CD117⁺Lin^– population (f). g BP-Combo did not change the lengths of ileum villi. H&E staining of the ileum villi are shown (left panel) and the villi lengths were calculated (right panel). Scale bar, 25 μm. BP-Combo did not affect the size and tissue structure of kidney (h) and heart (i). Scale bar, 50 μm (h, i). j BP-Combo did not influence mouse body weight. For b–j, samples/mice from a were subjected to the indicated analyses. k The working model of synergistic interaction between proteasome and WEE kinase inhibitors. Student’s t test (b–g) and two-way ANOVA (j) were used. *P < 0.05; **P < 0.01; ****P < 0.0001; ns not significant