Back to Search
Start Over
COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumour growth, metastasis and mortality, without compromising analgesia
- Source :
- British Journal of Cancer
- Publication Year :
- 2007
- Publisher :
- Springer Science and Business Media LLC, 2007.
-
Abstract
- Morphine and its congener opioids are the main therapy for severe pain in cancer. However, chronic morphine treatment stimulates angiogenesis and tumour growth in mice. We examined if celecoxib (a cyclooxygenase-2 (COX-2) inhibitor) prevents morphine-induced tumour growth without compromising analgesia. The effect of chronic treatment with celecoxib (by gavage) and/or morphine (subcutaneously), or PBS on tumour prostaglandin E(2) (PGE(2)), COX-2, angiogenesis, tumour growth, metastasis, pain behaviour and survival was determined in a highly invasive SCK breast cancer model in A/J mice. Two weeks of chronic morphine treatment at clinically relevant doses stimulates COX-2 and PGE(2) (4.5-fold compared to vehicle alone) and angiogenesis in breast tumours in mice. This is accompanied by increased tumour weight ( approximately 35%) and increased metastasis and reduced survival. Co-administration of celecoxib prevents these morphine-induced effects. In addition, morphine and celecoxib together provided better analgesia than either agent alone. Celecoxib prevents morphine-induced stimulation of COX-2, PGE(2), angiogenesis, tumour growth, metastasis and mortality without compromising analgesia in a murine breast cancer model. In fact, the combination provided significantly better analgesia than with morphine or celecoxib alone. Clinical trials of this combination for analgesia in chronic and severe pain in cancer are warranted.
- Subjects :
- Cancer Research
Angiogenesis
Pharmacology
Metastasis
Neovascularization
angiogenesis
Mice
0302 clinical medicine
030202 anesthesiology
Neoplasm Metastasis
Sulfonamides
Behavior, Animal
Morphine
Neovascularization, Pathologic
Drug Synergism
Tumor Burden
3. Good health
Analgesics, Opioid
Oncology
cyclooxygenase-2
030220 oncology & carcinogenesis
COX-2 inhibitor
Female
lipids (amino acids, peptides, and proteins)
medicine.symptom
medicine.drug
medicine.medical_specialty
Blotting, Western
Pain
Mammary Neoplasms, Animal
Mice, Inbred Strains
Dinoprostone
03 medical and health sciences
breast cancer
Breast cancer
Internal medicine
medicine
metastasis
Animals
Analysis of Variance
Cyclooxygenase 2 Inhibitors
business.industry
opioids
Cancer
medicine.disease
Endocrinology
Celecoxib
Cyclooxygenase 2
Pyrazoles
Analgesia
Translational Therapeutics
business
Subjects
Details
- ISSN :
- 15321827 and 00070920
- Volume :
- 97
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....1b2202d635a8ecb47afa073fd57cf331