Figure 6. Fluvastatin overcomes apoptotic resistance to MEK inhibitors in a mevalonate pathway-dependent manner in SK-MEL-28 and A549 cells.

(A) The phosphorylation status of Akt after the combined treatment of trametinib with fluvastatin in SK-MEL-28 cells. Cells were treated with trametinib (5 nM) and/or fluvastatin (1 μM) for 48 h, and the phosphorylated Akt was analyzed by Western blotting. (B) The sub-G1 populations after the combined treatment of trametinib with fluvastatin in SK-MEL-28 cells. Cells were treated with trametinib (5 nM) and/or fluvastatin (1 μM) for 72 h. DNA contents of the cells were analyzed by flow cytometer. Columns, means of triplicate data; bars, SD; ^**, P < 0.01 (C) The phosphorylation status of Akt after the combined treatment of trametinib with fluvastatin in A549 cells. Cells were treated with trametinib (40 nM) and/or fluvastatin (2 μM) for 48 h, and the phosphorylated Akt was analyzed by Western blotting. (D) The sub-G1 populations after the combined treatment of trametinib with fluvastatin in A549 cells. Cells were treated with trametinib (40 nM) and/or fluvastatin (2 μM) for 72 h. DNA contents of the cells were analyzed by flow cytometer. Columns, means of triplicate data; bars, SD; ^**, P < 0.01 (E) The sub-G1 populations after the combined treatment of trametinib with fluvastatin in the absence or presence of mevalonate. SK-MEL-28 cells were treated with trametinib (5 nM) and fluvastatin (1 μM) for 72 h with or without mevalonate (50 μM). DNA contents of the cells were analyzed by flow cytometer. Columns, means of triplicate data; bars, SD; ^**, P < 0.01 (F) The sub-G1 populations after the combined treatment of trametinib with fluvastatin in the absence or presence of mevalonate. A549 cells were treated with trametinib (40 nM) and fluvastatin (2 μM) for 72 h with or without mevalonate (50 μM). DNA contents of the cells were analyzed by flow cytometer. Columns, means of triplicate data; bars, SD; ^**, P < 0.01.