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Fig. 7 | Molecular Cancer

Fig. 7

From: CircNFIB inhibits tumor growth and metastasis through suppressing MEK1/ERK signaling in intrahepatic cholangiocarcinoma

Fig. 7

cNFIB enhances anti-tumor effects of trametinib in vivo. (A) Representative images of subcutaneous xenografts. RBE cells stably expressing vector or cNFIB were subcutaneously injected into the node mice. Mice were then dosed orally with or without trametinib once daily at 1 mg/kg for 15 consecutive days when subcutaneous tumor reached a volume of 100–130 mm3. Subcutaneous tumors were excised from node mice at day 15 after trametinib treatment. (B) Tumor weight and volume of subcutaneous xenografts. (C) Quantitative analysis of IHC staining of Ki-67 and p-ERK in xenografts. (D) Liver orthotopic-implantation models were established by injecting with indicated cells. Mice were then dosed orally with or without trametinib once daily at 1 mg/kg for 15 consecutive days from the 5th week after this model establishment; left, representative bioluminescent images of liver orthotopic-implantation models; right, quantitative analysis of liver photon flux emitted from the mice. (E) Lung metastasis models were established by injecting with indicated cells via tail vein. Mice were then dosed orally with or without trametinib once daily at 1 mg/kg for 15 consecutive days from the 7th week after this model establishment. Representative bioluminescent images of lung metastasis models (top), HE staining (middle), and of Ki-67 and p-ERK staining (bottom) of lung metastatic foci. (F) Quantitative analysis of total lung photon flux emitted from the mice, Ki-67 and p-ERK staining of lung metastatic lesions. (G) A proposed model illustrating inhibitory effects of cNFIB on ICC progression. cNFIB prevented the interaction between MEK1 and ERK by competitively binding to MEK1, thereby inactivating ERK phosphorylation. Frequent loss of cNFIB stimulated ERK phosphorylation to promote tumor cell proliferation, migration and invasion, finally inducing unfavorable prognosis of patients with ICC. Data were shown as mean ± SD, unpaired Student’s t test, *P < 0.05; **P < 0.01; ***P < 0.001

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