Differentiation and growth inhibition mediated via the RXR:PPARgamma heterodimer in colon cancer.
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.
Cesario
Rosemary M
RM
Department of Molecular Oncology, Ligand Pharmaceuticals, San Diego, CA 92121, USA. rcesario@ligand.com
Stone
Jessica
J
Yen
Wan-Ching
WC
Bissonnette
Reid P
RP
Lamph
William W
WW
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000077610:Bexarotene; D002454:Cell Differentiation; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000378:metabolism; D047488:Retinoid X Receptors / Q000819:agonists / Q000378:metabolism*; D000077154:Rosiglitazone; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D005343:Fibrinolytic Agents; D008565:Membrane Proteins; D047495:PPAR gamma; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077610:Bexarotene; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015230:Prostaglandin D2