Inhibition of P-Selectin and PSGL-1 Using Humanized Monoclonal Antibodies Increases the Sensitivity of Multiple Myeloma Cells to Bortezomib

Figure 4

Inhibition of P-selectin in combination with bortezomib decreases tumor size and improves survival in MM mouse model in vivo. The effect of P-selectin and PSGL-1 inhibition on sensitivity to bortezomib of the MM-bearing mice. SCID mice ( per group) were injected with MM1.s-GFP-Luc and tumor growth was determined by bioluminescence imaging (BLI). In the first experiment (c and d), tumor was allowed to grow for 3 weeks. The mice were then divided into 3 groups: (1) vehicle control; (2) anti-mouse P-selectin antibody (5 mg/kg); and (3) SelK2 and anti-mouse PSGL-1 (5 mg/kg). Tumor progression was monitored by BLI once a week for 4 weeks (week 3 = time 0). In the second experiment (a and b), tumor was allowed to grow for 2 weeks and then the mice were divided randomly into 4 groups: (1) vehicle control; (2) bortezomib alone (1 mg/kg); (3) bortezomib (1 mg/kg) + anti-mouse P-selectin antibody (5 mg/kg); and (4) bortezomib (1 mg/kg) + SelK2 and anti-mouse PSGL-1 (5 mg/kg). Tumor progression was monitored by BLI twice a week for 4 weeks (week 2 = time 0). Tumor progression was detected shown as region of interest (ROI) normalized to initial tumor size in each group; the statistical significance was assessed by student -test. The statistical significance was present between groups: vehicle versus bortezomib , vehicle versus P-sel + bortezomib , vehicle versus PSGL-1 + bortezomib , bortezomib versus P-sel + bortezomib , and P-sel + bortezomib versus PSGL-1 + bortezomib (a). Survival of mice was followed 40 days after starting the treatment and depicted as Kaplan-Meier curve. The values were calculated from the chi-squared test for independence. The statistical significance was present between groups: vehicle versus P-sel + bortezomib and bortezomib versus P-sel + bortezomib (b).

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