Figure 6
Figure 6. Perifosine inhibits human WM cell growth in vivo. (A) Immunodeficient irradiated SCID mice were inoculated subcutaneously in the flank with 3 × 106 BCWM.1 cells in 100 μL RPMI 1640 medium. Oral perifosine was administered daily (35 mg/kg per day) starting after the development of measurable tumors (N = 11). Perifosine significantly inhibited WM cell growth at week 12 (P = .04) compared with the control group (N = 8) treated with vehicle only (water). Error bars represent the variation in tumor volume for the mice per group. (B) Tumor tissues from mice treated with control vehicle (N = 2) or daily perifosine (N = 2) were harvested, processed, and subjected to Western blotting using anti-Akt, –p-Akt, –p-S6R and –β-actin antibodies. Adhesion and migration in vitro and homing in vivo. (C) Transwell migration assay showing inhibition of migration of BCWM.1 in the presence of perifosine 1 to 5 μM. SDF-1 30 nM was placed in the lower chambers and induced migration as compared with control with no SDF-1 (CTL, control). SDF-1 was placed in the lower chambers of the perifosine-treated wells. (D) Adhesion assay with BCWM.1 in the presence or absence of perifosine 2 to 10 μM. BCWM.1 demonstrated increased adhesion in fibronectin-coated wells (CTL, control) as compared with BSA-coated wells. Perifosine inhibited adhesion in fibronectin-coated wells in a dose-dependent manner. All data represent mean (± SD) of triplicate experiments (C,D). (E) In vivo flow cytometry. DID-labeled cells, either treated with perifosine 5 μM () or untreated control (), were injected in the tail vein of 2 balb/c mice. Cells were counted every 5 minutes for 1 hour. The cell count decreased by 75% in the control and only by 40% in the treated mouse, P = .001. (F) Histogram showing that the number of cells present in the perivascular bone marrow niches of the skull was significantly higher in the control mice compared with the perifosine-treated group at 24 hours after injection (P = .039), using in vivo confocal imaging of quadrants 3 and 4 of the skull of mice.

Perifosine inhibits human WM cell growth in vivo. (A) Immunodeficient irradiated SCID mice were inoculated subcutaneously in the flank with 3 × 106 BCWM.1 cells in 100 μL RPMI 1640 medium. Oral perifosine was administered daily (35 mg/kg per day) starting after the development of measurable tumors (N = 11). Perifosine significantly inhibited WM cell growth at week 12 (P = .04) compared with the control group (N = 8) treated with vehicle only (water). Error bars represent the variation in tumor volume for the mice per group. (B) Tumor tissues from mice treated with control vehicle (N = 2) or daily perifosine (N = 2) were harvested, processed, and subjected to Western blotting using anti-Akt, –p-Akt, –p-S6R and –β-actin antibodies. Adhesion and migration in vitro and homing in vivo. (C) Transwell migration assay showing inhibition of migration of BCWM.1 in the presence of perifosine 1 to 5 μM. SDF-1 30 nM was placed in the lower chambers and induced migration as compared with control with no SDF-1 (CTL, control). SDF-1 was placed in the lower chambers of the perifosine-treated wells. (D) Adhesion assay with BCWM.1 in the presence or absence of perifosine 2 to 10 μM. BCWM.1 demonstrated increased adhesion in fibronectin-coated wells (CTL, control) as compared with BSA-coated wells. Perifosine inhibited adhesion in fibronectin-coated wells in a dose-dependent manner. All data represent mean (± SD) of triplicate experiments (C,D). (E) In vivo flow cytometry. DID-labeled cells, either treated with perifosine 5 μM () or untreated control (), were injected in the tail vein of 2 balb/c mice. Cells were counted every 5 minutes for 1 hour. The cell count decreased by 75% in the control and only by 40% in the treated mouse, P = .001. (F) Histogram showing that the number of cells present in the perivascular bone marrow niches of the skull was significantly higher in the control mice compared with the perifosine-treated group at 24 hours after injection (P = .039), using in vivo confocal imaging of quadrants 3 and 4 of the skull of mice.

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