Figure 7. Disrupting the Notch pathway with MRK-003 reduces osteolytic bone metastasis.

(A) Normalized BLI signals of bone metastasis in mice (n=10) that have been injected with SCP2 cells and treated with vehicle or MRK-003. *p < 0.05, ** p < 0.005.

(B) BLI and X-ray images of bone lesions from four representative mice in each experimental group.

(C) Kaplan-Meier bone metastasis-free survival curve of mice from each experimental group.

(D) Quantification of total and hind limb bone lesions in vehicle or MRK003-treated mice. *p < 0.05.

(E) Quantification of radiographic osteolytic lesion area of hind limbs of mice from each experimental group.

(F) Quantification of TRAP⁺ osteoclasts along the bone-tumor interface of metastases of mice from each experimental group.

(G) Histological (H&E and TRAP staining) analysis of bone metastases from each experimental group. Arrowheads indicate bone destruction in histological sections of vehicle mice. Scale bar = 200 μM.

(H) qRT-PCR mRNA expression of Notch target genes and mouse IL-6 in the stromal compartment of bone metastasis from vehicle or MRK-003-treated mice using mouse-specific primers. *p < 0.005, **p < 0.001.

Data in the figure represent average ± SEM; p-values were based on Student’s t-test unless otherwise indicated.