Growth inhibition of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors by controlled-release low-dose medroxyprogesterone acetate.
Since our previous findings had indicated that the androgenic steroid medroxyprogesterone acetate (MPA) exerts potent inhibitory effects on 7,12-dimethylbenz(a)anthracene (DMBA)-induced tumor growth, we have studied the effect of low doses of MPA released from Depo-Provera and from 50:50 poly[DL-lactide-co-glycolide] microspheres in the same DMBA-induced tumor model. The present data show that single subcutaneous injection of a 4-month controlled-release formulation of biodegradable 50:50 poly[DL-lactide-co-glycolide] microspheres containing 10 mg of MPA giving serum levels of 3.14 +/- 0.32 ng/ml (8.12 +/- 0.83 nM) MPA causes a maximal or near-maximal 60% inhibition of tumor growth measured 56 days later. Such data suggest that controlled-release formulations giving constant and low blood levels of MPA could be used for the treatment of breast cancer in women. Such a low concentration of MPA should avoid the side effects observed with the high doses of the compound.
Li
S
S
Medical Research Council of Canada Group in Molecular Endocrinology, CHUL Research Center, Québec, Canada.
Lepage
M
M
Mérand
Y
Y
Bélanger
A
A
Labrie
F
F
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002277:Carcinoma / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D003692:Delayed-Action Preparations; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007279:Injections, Subcutaneous; D007986:Luteinizing Hormone / Q000097:blood; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage* / Q000097:blood; D008863:Microspheres; D051381:Rats; D017207:Rats, Sprague-Dawley
D003692:Delayed-Action Preparations; D015127:9,10-Dimethyl-1,2-benzanthracene; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D017258:Medroxyprogesterone Acetate