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Chemoprevention of Colon Cancer through Inhibition of Angiogenesis and Induction of Apoptosis by Nonsteroidal Anti-Inflammatory Drugs.
- Source :
-
Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer [J Environ Pathol Toxicol Oncol] 2016; Vol. 35 (3), pp. 273-289. - Publication Year :
- 2016
-
Abstract
- Cancer cells require nourishment for the growth of the primary tumor mass and spread of the metastatic colony. These needs are fulfilled by tumor-associated neovasculature known as angiogenesis, which also favors the transition from hyperplasia to neoplasia, that is, from a state of cellular multiplication to uncontrolled proliferation. Therefore, targeting angiogenesis is profitable as a mechanism to inhibit tumor growth. Furthermore, it is important to understand the cross-communication between vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in the neoplastic and proinflammatory milieu. We studied the role of two important chemokines (monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-1β [MIP-1β]) along with VEGF and MMPs in nonsteroidal anti-inflammatory drug (NSAID)-induced chemopreventive effects in experimental colon cancer in rats. 1,2-Dimethylhydrazine dihydrochloride (DMH) was used as cancer-inducing agent and three NSAIDs (celecoxib, etoricoxib, and diclofenac) were given orally as chemopreventive agents. Analysis by immunofluorescence and western blotting shows that the expression of VEGF, MMP-2, and MMP-9 was found to be significantly elevated in the DMH- treated group and notably lowered by NSAID coadministration. The expression of MCP-1 was found to be markedly decreased, whereas that of MIP-1β increased after NSAID coadministration. NSAID coadministration was also able to induce apoptosis, confirmed using studies by Hoechst/propidium iodide (PI) costaining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Results from the present study indicate the potential role of these chemokines along with VEGF and MMPs against angiogenesis in DMH-induced cancer. The inhibition of angiogenesis and induction of apoptosis by NSAIDs were found to be possible mechanisms in the chemoprevention of colon cancer.
- Subjects :
- Animals
Anti-Inflammatory Agents, Non-Steroidal therapeutic use
Celecoxib pharmacology
Celecoxib therapeutic use
Colonic Neoplasms etiology
Diclofenac pharmacology
Diclofenac therapeutic use
Etoricoxib
Female
Neovascularization, Pathologic etiology
Pyridines pharmacology
Pyridines therapeutic use
Rats
Rats, Sprague-Dawley
Sulfones pharmacology
Sulfones therapeutic use
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Anticarcinogenic Agents pharmacology
Apoptosis drug effects
Colonic Neoplasms drug therapy
Cyclooxygenase 2 Inhibitors pharmacology
Neovascularization, Pathologic drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 2162-6537
- Volume :
- 35
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 27910782
- Full Text :
- https://doi.org/10.1615/JEnvironPatholToxicolOncol.2016015704