Chemopreventive efficacies of rosiglitazone, fenretinide and their combination against rat mammary carcinogenesis.
BACKGROUND
Peroxisome proliferator-activated receptor gamma (PPAR-gamma) and retinoic acid receptors (RAR/RXR) belong to the nuclear steroid receptor family. In vitro studies have suggested that PPAR-gamma ligands are highly effective in preventing mammary tumours and these effects are enhanced by some retinoids. However, in vivo anti-initiator and anti-promoter efficacies of this combination are not clear.


OBJECTIVE
The present study aimed to investigate the chemopreventive efficacies of the PPAR-gamma ligand rosiglitazone (200 microg/kg/day), synthetic retinoid fenretinide (0.3 mg/kg/day) and their combination on a DMBA-induced rat mammary carcinogenesis model.


RESULTS
In the rosiglitazone group, no malignant tumour developed, apart from the lowest proliferative mammary lesions. In the fenretinide group, 30% developed a malignant tumour but there were no benign tumours. Cancer incidences were 61.5% and 10% in the control and combination groups respectively.


CONCLUSIONS
Our results showed that the PPAR-gamma ligand rosiglitazone and synthetic retinoid fenretinide have potent chemopreventive properties against in vivo mammary carcinogenesis; however, the efficacies were not enhanced by their combination.
Kocdor
Hilal
H
Institute of Oncology, Dokuz Eylul University, Inciralti, Izmir, Turkey. hilal.kocdor@deu.edu.tr
Kocdor
Mehmet Ali
MA
Canda
Tulay
T
Gurel
Duygu
D
Cehreli
Ruksan
R
Yilmaz
Osman
O
Alakavuklar
Mehmet
M
Guner
Gul
G
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002273:Carcinogens / Q000633:toxicity; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000097:blood; D005260:Female; D017313:Fenretinide / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D002273:Carcinogens; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D017313:Fenretinide; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; D007334:Insulin-Like Growth Factor I; D011388:Prolactin