Fig. 7: Inhibition of FBXO22 enhanced Lenvatinib sensitivity in vivo and in vitro.

A The effect of Lenvatinib on tubule formation of HUVECs was significantly increased by inhibiting FBXO22 expression in MHCC97H cells (left panel). Quantitative analysis of the effect of FBXO22 on Lenvatinib against tubule formation of HUVECs (right panel). B The suppressive impact of Lenvatinib on the expression of P-AKT(S473), HIF-1α, and VEGF-A were augmented following the knockdown of FBXO22. C Re-expressing FBXO22 could rescue the tubule formation of HUVECs cultured by CM of FBXO22 knockdown MHCC97H cells. D Schematic diagram of AAV8 administration and Lenvatinib gavage in nude mice with orthotopic MHCC97H-luciferase cells. E The expression level of FBXO22 protein in tumor tissue. F The bioluminescence and liver with tumor images of orthotopically injected HCC MHCC97H-luciferase cells in nude mice, following self-complementary AAV8 (scAAV8)-U6-shNC/shFBXO22 administration in combination with Lenvatinib for 40 days. The quantitative results of tumor bioluminescence and volume are shown. G Representative images of H&E and IHC as well as quantitative results for CD31 and VEGF-A from intrahepatic model. Data and error bars are presented as mean ± SD from triplicate independent replicate experiments. The data were analyzed using a paired Student’s t-test for experiments (C, F, G). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.