Abstract
This study evaluated the anti-tumor efficacy of combining the RXR agonist, bexarotene, with the PPARgamma agonist, rosiglitazone, in colon cancer. Moser, a human colon cancer cell line, was treated with bexarotene and rosiglitazone alone or in combination and the effect on growth and differentiation were examined. The data demonstrated that the bexarotene/rosiglitazone combination produced greater efficacy in growth inhibition than either single agent. Furthermore, combination treatment acted cooperatively to decrease COX-2 expression and PGE2 synthesis while increasing expression of the differentiation marker, CEA. These findings were confirmed in vivo in a Moser xenograft tumor model. Collectively, our data suggest a potential role for utilizing a combination regimen of a RXR and PPARgamma agonist in the treatment of colon cancer.
MeSH terms
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Animals
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Anticarcinogenic Agents / pharmacology
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Bexarotene
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Cell Differentiation*
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Cell Proliferation*
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Colonic Neoplasms / drug therapy
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Colonic Neoplasms / metabolism*
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Colonic Neoplasms / pathology*
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Cyclooxygenase 2 / metabolism
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Fibrinolytic Agents / pharmacology
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Humans
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Male
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Membrane Proteins / metabolism
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Mice
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Mice, Nude
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PPAR gamma / agonists
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PPAR gamma / metabolism*
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Prostaglandin D2 / metabolism
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Retinoid X Receptors / agonists
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Retinoid X Receptors / metabolism*
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Rosiglitazone
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Tetrahydronaphthalenes / pharmacology
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Thiazolidinediones / pharmacology
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Transplantation, Heterologous
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Tumor Cells, Cultured
Substances
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Anticarcinogenic Agents
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Fibrinolytic Agents
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Membrane Proteins
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PPAR gamma
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Retinoid X Receptors
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Tetrahydronaphthalenes
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Thiazolidinediones
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Rosiglitazone
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Bexarotene
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin D2