Fig. 6: Down-regulating CNOT3 overcomes gefitinib resistance and inhibits metastatic progression in vivo. | Cell Death Discovery

Fig. 6: Down-regulating CNOT3 overcomes gefitinib resistance and inhibits metastatic progression in vivo.

From: Targeting the up-regulated CNOT3 reverses therapeutic resistance and metastatic progression of EGFR-mutant non-small cell lung cancer

Fig. 6

A, B PC-9 GR2 cells transfected with the CNOT3-specific shRNA Tet-on inducible plasmid were treated with DOX (2.5 μg/ml) for 48 h. Cells were subjected to western blotting to assess protein expression levels (A). CNOT3 mRNA levels in cells were measured by q-PCR (B). C–G BALB/c nude mice were inoculated with PC-9 GR2 cells harboring CNOT3-specific shRNA Tet-on inducible plasmid. A schematic view of the treatment plan (C). Plots of tumor volumes (D). Summary of volume data of tumors harvested after euthanizing the mice (E). Images of tumors harvested after euthanizing the mice (F). Representative images of HE and immunohistochemical staining of Keratin 7 expression in the lymph nodes harvested from mice treated with gefitinib (G). H A model of the c-Jun/CNOT3 feedback loop dysregulation contributes to gefitinib resistance and tumor progression. Data are shown as the mean±S.E.M. n = 4. B Student’s t-test. D Two-way ANOVA and Bonferroni post hoc test. E One-way ANOVA with Tukey post hoc test. ***P < 0.001, **P < 0.01 or *P < 0.05 for comparisons between the indicated groups.

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