Fig. 4.

Synergistic antitumor effects of RNF183 knockdown and trametinib treatment on xenograft tumor growth of HCT116 cells. a A representative image of tumors collected from mice inoculated with HCT116 cells that were stably transfected with shRNF183 or shNC and treated with or without trametinib. When tumor reached 100 mm³, 6 mice respectively from the shRNF183 or shNC groups were given 300 μg/kg trametinib every day for 23 days. The remaining 6 mice in each group were treated with vehicle as control. b RNF183 knockdown and trametinib synergistically reduced tumor volumes (i) and tumor weights (ii). c qPCR assay results show that the IL-8 levels in xenograft tumors were synergistically repressed by RNF183 knockdown and trametinib treatment. d Images exhibiting the hematoxylin–eosin (H&E), RNF183, and Ki-67 staining for xenograft tumors, which indicate decreased intensity of Ki-67 in RNF183-knockdown, trametinib treatment, and combination treatment groups. RNF183 is located in the cytoplasm and nucleus and Ki-67 is located in the nucleus. ***P < 0.001