Figure 6. Combined inhibition of Pim and PI3K/Akt/mTOR pathways suppresses the growth of K562 tumor engrafted in nude mice in a synergistic manner.

A. nude mice carrying K562 xenografts were treated with SMI-4a (50 mg/kg) alone, Akti-1/2 (80 mg/kg) alone, their combination, or vehicle control every other day. Tumors were excised at 8 h after the last treatment. Shown are representatives from six independent experiments. B. plotted are relative volumes of tumors in A. The average volume of vehicle control was set as 100%. Error bars, SEM, n = 24 (**P < 0.01). C. eIF4B Ser422 phosphorylation in representative tumors in A was examined by immunoblotting. D. levels of phosphorylated eIF4B in C were quantitated by densitometry, and normalized to total eIF4B levels. The levels of Ser422 phosphorylation of Mock group were 100%. Plotted are results from three independent experiments. Error bars represent SEM, n = 3 (**P < 0.01). E. nude mice bearing GFP-expressing K562 xenografts were treated with SMI-4a (50 mg/kg) alone, rapamycin (10 mg/kg) alone, combined treatment, or vehicle control every other day. Tumors were excised at 8 hours after the last treatment. Shown are representatives from five independent experiments. F. shown are relative volumes of tumors in E. The average volume of vehicle control was set as 100%. Error bars, SEM, n = 20 (**P < 0.01). G. over a 21-day period after xenograft inoculation, tumors under indicated treatments were measured by bioluminescent imaging. Shown are representative images from at least three independent experiments with similar results. H. tumors in E were examined by immunoblotting with indicated antibodies. I. levels of phosphorylated eIF4B in H were quantitated by densitometry, and normalized to total eIF4B levels as described in D.