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Updated: Aug 18, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
The effect of cyclooxygenase-2 (COX-2) inhibition on human prostate cancer induced osteoblastic and osteolytic
Seth C Gamradt1, Brian T Feeley, Nancy Q Liu
1Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Background:
The mechanism of bone formation by osteoblastic prostate cancer metastases is not well defined. Using knockout mice, it has been demonstrated that prostaglandins produced by COX-2 are critical for fracture repair. Therefore, our aim was to determine if COX-2 plays a role in the bone formation in osteoblastic prostate cancer metastases in bone.
Materials And Methods:
We assessed the influence of pharmacologic COX-2 inhibition in a SCID mouse intratibial injection model of bone metastasis using two human prostate cancer cell lines that produce either osteoblastic lesions (LAPC-9) or osteolytic lesions (PC-3, negative control). SC-58236, a COX-2 specific inhibitor, was used at a dose of 3 mg/Kg intraperitoneally 3 times per week in the Treatment groups for 8 weeks until sacrifice.
Results:
Western blot for COX-2 demonstrated that LAPC-9 cells expressed high levels of COX-2 while PC-3 cells did not. Treatment with SC-58236 significantly reduced the size of osteoblastic lesions after LAPC-9 injection based on both radiographic and histomorphometric criteria compared to the control group. In contrast, large osteolytic lesions were seen in both control and SC-58236 treated animals after PC-3 cell injections. The results of this study indicate that COX-2 inhibition can decrease the size of osteoblastic lesions produced by LAPC-9, a human prostate cancer cell line that expresses high levels of COX-2. This treatment had no effect on the osteolytic activity of PC-3 cells.
Conclusion:
These findings suggest that the progression of osteoblastic metastases induced by human prostate cancer cells may be limited by COX-2 inhibitors.
Insights
Cyclooxygenase-2 (COX-2) inhibitors reduced osteoblastic prostate cancer bone metastases size in mice. This suggests COX-2 inhibitors may limit the progression of these bone lesions.
Area of Science:
- Oncology
- Orthopedics
- Pharmacology
Background:
- The mechanism of osteoblastic bone formation by prostate cancer metastases is not fully understood.
- Prostaglandins produced by COX-2 are crucial for fracture repair, suggesting a potential role in bone metastasis.
Purpose of the Study:
- To investigate the role of COX-2 in the bone formation of osteoblastic prostate cancer metastases.
- To determine if COX-2 inhibition affects osteoblastic and osteolytic bone lesions in prostate cancer metastasis models.
Main Methods:
- A SCID mouse model of bone metastasis was used with human prostate cancer cell lines (LAPC-9 for osteoblastic, PC-3 for osteolytic).
- Mice received SC-58236, a COX-2 specific inhibitor, or a control treatment for 8 weeks.
- Osteoblastic and osteolytic lesions were assessed using radiographic and histomorphometric analyses.
Main Results:
- LAPC-9 cells expressed high levels of COX-2, while PC-3 cells did not.
- SC-58236 treatment significantly reduced the size of osteoblastic lesions in LAPC-9 injected mice.
- COX-2 inhibition did not affect the osteolytic lesions produced by PC-3 cells.
Conclusions:
- COX-2 plays a significant role in the development of osteoblastic prostate cancer bone metastases.
- COX-2 inhibitors show potential for limiting the progression of osteoblastic bone metastases.
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