Figure 5. Therapeutic reactivation of PP2A suppresses PNET growth in vivo.

(A) BON-1 cells (5 × 10⁶) were injected subcutaneously into NOD.SCID mice. Once tumors reached an average volume of 200 mm³, drug treatments were initiated. Tumor volumes were measured over a 4-week period in which mice were treated by oral gavage with vehicle control, SMAP (5 mg/kg, twice a day), MK-2206 (30 mg/kg, 3 times a week), and a combination of SMAP plus MK-2206. SEM for at least n = 5 mice per group; *P < 0.03 for vehicle versus SMAP or SMAP+MK-2206; #P < 0.05 for vehicle versus MK-2206; 2-way ANOVA and adjusted for multiple comparisons using Bonferroni method. (B) Comparison of tumor weights from vehicle (V), SMAP (S), MK-2206 (M), and SMAP plus MK-2206 (S+M) groups after the final treatment. Error bars, SEM; *P < 0.001, 2-way ANOVA and adjusted for multiple comparisons using the Bonferroni method. (C) Representative Western blot analyses of the indicated proteins in lysates of xenografted BON-1 tumors harvested from the treated mice. (D–F) Quantification of relative levels of RABL6A, pAKT-S473, and pRB1-S807/811 in xenograft tumors, respectively, obtained by ImageJ analysis of Western blots (as shown in C). Mean ± SEM; *P < 0.05; **P < 0.01; 2-way ANOVA and adjusted for multiple comparisons using the Bonferroni method. (G) Representative H&E and IHC staining for the indicated proteins in BON-1 xenograft tumors from vehicle control and SMAP-treated mice. Images were taken at ×400. (H) Quantification of pAKT-S473 staining (assessed as weak = 1, moderate = 2, strong = 3) in tumors from vehicle-treated (V) and SMAP-treated (S) mice. Mean ± SEM; *P < 0.001, Student’s t test.