Fig. 5: Trametinib sensitize HCC treatment with NF1 loss through ERK and AKT reactivation.
From: Genome-scale CRISPR-Cas9 knockout screening in hepatocellular carcinoma with lenvatinib resistance
A Trametinib was the most sensitive drug for the loss of Huh7 NF1 or DUSP9 cells. The IC50 value of trametinib toward the Huh7 NF1 sgRNA or DUSP9 sgRNA cells was significantly lower than that of Az628, VTX-11e, and SHP009. B Trametinib could inhibit colony formation capacities from those in NF1 or DUSP9 knockout cells. C Trametinib was still able to halt HCC growth when NF1 was knocked out. The tumor weight and volume were significantly decreased after lenvatinib or trametinib treatment. However, the tumor weights or volumes of NF1 sgRNA cell-injected mice were significantly higher than those of tumors without NF1 knockout cells after lenvatinib treatment, and trametinib treatment did not show any difference in both. D The ERK and AKT phosphorylation was sustained in the presence of trametinib in Huh7 cells. Error bars represent mean ± SEM for triplicate experiments, *P < 0.05, **P < 0.01, ***P < 0.001, ns no significantly changed.
