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. Author manuscript; available in PMC: 2017 Sep 15.
Published in final edited form as: Cancer Res. 2016 Aug 3;76(18):5455–5466. doi: 10.1158/0008-5472.CAN-15-3384

Figure 3. Sensitivity to combined CDK4/6 and MEK inhibition is associated with survivin depletion in sensitive cells.

Figure 3

A. Representative annexin V staining of melanoma lines treated with trametinib (5 nM) and palbociclib (0.5 μM) treatment alone or a combination of both compounds for 48 hours (n=3, error bars=SD from triplicate samples, *p<0.05). B. A375 cells were treated with single agent or combination of trametinib and palbociclib for 24 hours. Lysates were analyzed by RPPA. The heatmap shows the most significantly regulated proteins (p<0.01). C. Elevated levels of Bim-EL in trametinib and combo-treated lysates. D. 1205Lu cells were transfected with siRNA to Bim in the presence or absence of trametinib and palbociclib. Knockdown of Bim rescued apoptotic phenotype elicited by trametinib and palbociclib treatments. E. Fold change in BIRC5/survivin regulation after 24 hours of treatment with indicated inhibitors. Two independent sets of tests were carried out and representative data is shown. F. Western blotting for survivin in resistant (CHL-1, Bowes, SKMEL207) and sensitive (A375, WM793, 1205Lu, SBcl2, WM1346, WM1366) cell lines in basal state as well as following treatment with trametinib and/or palbociclib for 48 hours. G. NRAS mutant melanoma tumor explant treated with DMSO, trametinib (50 nM), palbociclib (0.5 μM) or the combination.