Figure 4. In Vivo Efficacy of Combined BCL-XL and MEK Inhibition.
(A) KRAS mutant xenografts were treated with vehicle (CON), ABT-263 (ABT, 100 mg/kg daily), selumetinib (SEL, 25 mg/kg twice daily), or both drugs in combination. The mean percent change in tumor volume relative to initial tumor volume is shown. Error bars represent SEM.
(B) Waterfall plot showing the percent change in tumor volume (relative to initial volume) for individual tumors in the SEL and ABT/SEL groups following 21 days of treatment. P values were generated by two-tailed t test.
(C) Tumor tissue from HCT116 xenografts treated for 3 days with the indicated drug regimens was evaluated by immunohistochemistry for P-ERK, Ki67 (a marker of proliferation), or cleaved caspase 3 (a marker of apoptosis). Tumors were harvested 3 hr after dosing on day 3. Scale bar represents 100 µm.
(D and E) Established lung tumors in LSL-KRASG12D mice were treated with vehicle, ABT, SEL, or both drugs in combination as in (A). (D) MR images of two mice obtained pretreatment and following 1 week of treatment with the ABT/SEL combination. Red arrows indicate dense areas of lung tumor in the pretreatment images. (E) Mean percent tumor regression of lung tumors following 2 weeks of the indicated treatment. p represents ABT/SEL versus each treatment group by one-way ANOVA with Tukey post-hoc test. All error bars represent SEM.
See also Figure S4.