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Anticancer Res. 2005 Jan-Feb;25(1A):107-15.

The effect of cyclooxygenase-2 (COX-2) inhibition on human prostate cancer induced osteoblastic and osteolytic lesions in bone.

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1
Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

Abstract

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.

PMID:
15816526
[Indexed for MEDLINE]
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