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Combination Treatment with MEK and AKT Inhibitors Is More Effective than Each Drug Alone in Human Non-Small Cell Lung Cancer In Vitro and In Vivo

Figure 5

Pharmacodynamic effects of AZD6244-MK2206 on A549 xenograft mouse models.

The xerograft mouse models were treated with vehicle control, AZD6244 (24 mg/kg), MK2206 (6 mg/kg) or AZD6244-MK2206 (24 mg/kg–6 mg/kg) combination for 3 days. Four hours after the last dose, the tumors were resected, fixed and paraffin-embedded. (A) The sections were analyzed by immunohistochemistry using p-ERK and p-AKT antibodies and the representative photographs in tumor sections are shown. (B) The sections were subjected to TUNEL and DAPI staining. The relative apoptotic cells were determined by counting TUNEL positive cells in five random fields (at 100× magnification) for each sample. Columns, mean; bar, SD. *, P<0.05, compared with the single agent treatments. The representative photographs in tumor sections are shown.

Figure 5

doi: https://doi.org/10.1371/journal.pone.0014124.g005