Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are emerging as novel chemopreventive agents because of their ability in blocking cellular proliferation, and thereby tumor development, and also by promoting apoptosis. GSK-3β, a serine threonine kinase and a negative regulator of the oncogenic Wnt/β-catenin signaling pathway, plays a critical role in the regulation of oncogenesis. Celecoxib and etoricoxib, the two cyclooxygenase-2 (COX-2) selective NSAIDs, and Diclofenac, a preferential COX-2 inhibitory NSAID, had shown uniformly the chemopreventive and anti-neoplastic effects in the early stage of colon cancer by promoting apoptosis as well as an over-expression of GSK-3β while down-regulating the PI3-K/Akt oncogenic pathway.
Keywords:
Akt; DMH; GSK-3β; PI3-K; colorectal cancer; β-catenin.
MeSH terms
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1,2-Dimethylhydrazine
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Animals
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Anticarcinogenic Agents / pharmacology*
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Apoptosis / drug effects
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Celecoxib / pharmacology
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Cell Transformation, Neoplastic / drug effects*
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Cell Transformation, Neoplastic / metabolism
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Cell Transformation, Neoplastic / pathology
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Colon / drug effects*
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Colon / enzymology
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Colon / pathology
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Colonic Neoplasms / chemically induced
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Colonic Neoplasms / enzymology
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Colonic Neoplasms / pathology
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Colonic Neoplasms / prevention & control*
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Cyclooxygenase 2 Inhibitors / pharmacology*
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Diclofenac / pharmacology
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Etoricoxib
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Female
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Glycogen Synthase Kinase 3 beta / metabolism*
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PTEN Phosphohydrolase / metabolism
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Phosphatidylinositol 3-Kinase / metabolism*
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Proto-Oncogene Proteins c-akt / metabolism*
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Pyridines / pharmacology
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Rats, Sprague-Dawley
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Sulfones / pharmacology
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Time Factors
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Wnt Signaling Pathway / drug effects*
Substances
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Anticarcinogenic Agents
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Cyclooxygenase 2 Inhibitors
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Pyridines
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Sulfones
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Diclofenac
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Phosphatidylinositol 3-Kinase
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Glycogen Synthase Kinase 3 beta
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Gsk3b protein, rat
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Proto-Oncogene Proteins c-akt
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PTEN Phosphohydrolase
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Pten protein, rat
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1,2-Dimethylhydrazine
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Celecoxib
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Etoricoxib