Research Paper Volume 16, Issue 17 pp 12277—12292

CIB2 mediates acquired gefitinib resistance by inducing ZEB1 expression and epithelial-mesenchymal transition

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Figure 7. CIB2 expression promotes tumorigenesis and gefitinib resistance in vivo. PC-9 or CIB2-overexpressed cells were injected into the flanks of nude mice. When the tumor volume reached about 50 mm3, gefitinib (10 mg/kg) or 0.9% saline was given by oral gavage every three days. Mice weights and tumor volumes of mice were recorded. After three weeks, the mice were anaesthetized, and tumor tissues were stripped out and then weighted. (A) Each group of tumors was taken out for photography and analysis. Tumor weights (B) and tumor sizes (C) were significantly larger in CIB2-overexpressed group, despite given gefitinib to the CIB2 group, the tumor weights and tumor volumes showed resistance to gefitinib treatment. Corresponding control (n = 4). Data were statistically analyzed using Student’s t-test and values were presented as mean ± SD of three independent experiments. ** and ***. *indicated significant difference at p < 0.05. (D) Body weights of mice in each group showed no significant changes during the drug treatment. (E) The immunohistochemistry results showed high Ki67 and CD34 expression levels in CIB2-overexpressed group than the control group, and the CIB2-overexpressed group treated with gefitinib showed slightly decreased Ki67 and CD34 expression levels. (F) A pattern diagram to summarize the role of CIB2 in the regulation of tumorigenesis and chemoresistance in lung cancer. CIB2/ZEB1 axis induced tumor growth and gefitinib resistance by inhibiting cell apoptosis and enhancing EMT in lung cancer.