Journal article
Effect of combined cyclooxygenase-2 and matrix metalloproteinase inhibition on Human sarcoma xenografts
Journal of pediatric hematology/oncology, Vol.25(9), pp.709-714
2003
DOI: 10.1097/00043426-200309000-00007
PMID: 12972806
Abstract
Purpose: Sarcomas express cyclooxygenase (COX)-2, an inducible enzyme with known tumor-promoting activity. COX-2 inhibition is efficacious against many cancer types but has not been tested for human sarcomas. Matrix metalloproteinase (MMP) inhibitors also possess antiproliferative activity. Because MMP inhibitor therapy induces COX-2 expression, the authors hypothesized that the combination of COX-2 and MMP inhibitors results in a synergistic antitumor effect.
Methods: Human osteosarcoma or rhabdomyosarcoma cells were injected into athymic mice. Tumor development and growth were measured following treatment with a COX-2 inhibitor (celecoxib), an MMP inhibitor (doxycycline), or both. The tumors were analyzed for necrosis, apoptosis, cyclooxygenase activity (PGE2 production), and MMP-2 levels.
Results: When treatment was started prior to tumor cell implantation, doxycycline inhibited osteosarcoma tumor growth alone and in combination with celecoxib (30% and 33% reduction, respectively). An effect on osteosarcoma tumor implantation rates was noted in mice receiving doxycycline alone and in combination with celecoxib (12.5% and 6.25% reduction, respectively). Established osteosarcoma and rhabdomyosarcoma tumors were inhibited only by combination therapy (36% and 55%, respectively). A higher proportion of osteosarcoma tumors in the combination therapy group had more than 50% necrosis (3/7) when compared with control tumors (0/8). Antitumor effects did not correlate with PGE2 levels, suggesting the observed interaction with doxycycline was due to previously described non-enzymatic effects of celecoxib.
Conclusions: The authors' preclinical data suggest that the combination of inexpensive, nontoxic, oral COX-2 and MMP inhibitors may be useful for the treatment of some types of solid tumors.
Details
- Title: Subtitle
- Effect of combined cyclooxygenase-2 and matrix metalloproteinase inhibition on Human sarcoma xenografts
- Creators
- David S DICKENS - Division of Pediatric Hematology/Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United StatesTimothy P CRIPE - Division of Pediatric Hematology/Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
- Resource Type
- Journal article
- Publication Details
- Journal of pediatric hematology/oncology, Vol.25(9), pp.709-714
- Publisher
- Lippincott
- DOI
- 10.1097/00043426-200309000-00007
- PMID
- 12972806
- ISSN
- 1077-4114
- eISSN
- 1536-3678
- Language
- English
- Date published
- 2003
- Academic Unit
- Stead Family Department of Pediatrics; Hematology/Oncology
- Record Identifier
- 9984093597402771
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