Figure 7
Figure 7. PCI-32765 inhibits MM cell growth and MM-induced bone lysis in a murine model of human MM. (A) SCID-hu mice were injected with INA-6 MM cells into the implanted human bone and continuously treated with PCI-32765 (12 mg/kg, n = 6) or vehicle control (n = 5) beginning after first detection of tumor by monitoring shuIL-6R in mouse serum samples weekly. (B) Bone chips were retrieved from SCID-hu mice, decalcified, and sectioned. Tissue slides were stained with H&E and immunohistochemically analyzed for CD138 (MM), TRAP (OC), and ALP (OB). Original magnification ×200, except for ALP (original magnification ×400). (C) Representative cross-sectional images by 3-dimensional reconstruction of the harvested human bones obtained after performing high-resolution micro-CT scan are shown and quantified (D). *P < .04. (E) Osteogenic activity per bone surface (ALP+/BS), indicating bone formation activity. **P < .01. The PCI-32765-treated group displayed significantly reduced osteolysis induced by MM cells and enhanced osteogenic activity, compared with vehicle control group. Effects of PCI-32765 were also quantitated in the left (mouse L) and right (mouse R) normal mouse extremities (F).

PCI-32765 inhibits MM cell growth and MM-induced bone lysis in a murine model of human MM. (A) SCID-hu mice were injected with INA-6 MM cells into the implanted human bone and continuously treated with PCI-32765 (12 mg/kg, n = 6) or vehicle control (n = 5) beginning after first detection of tumor by monitoring shuIL-6R in mouse serum samples weekly. (B) Bone chips were retrieved from SCID-hu mice, decalcified, and sectioned. Tissue slides were stained with H&E and immunohistochemically analyzed for CD138 (MM), TRAP (OC), and ALP (OB). Original magnification ×200, except for ALP (original magnification ×400). (C) Representative cross-sectional images by 3-dimensional reconstruction of the harvested human bones obtained after performing high-resolution micro-CT scan are shown and quantified (D). *P < .04. (E) Osteogenic activity per bone surface (ALP+/BS), indicating bone formation activity. **P < .01. The PCI-32765-treated group displayed significantly reduced osteolysis induced by MM cells and enhanced osteogenic activity, compared with vehicle control group. Effects of PCI-32765 were also quantitated in the left (mouse L) and right (mouse R) normal mouse extremities (F).

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