Additive inhibitory effects of bromocryptine (CB-154) and medroxyprogesterone acetate (MPA) on dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in the rat.
Treatment for 18 days of rats bearing dimethylbenz[a]anthracene-induced mammary tumors with the synthetic medroxyprogesterone acetate (MPA) or the inhibitor of prolactin secretion 2 alpha-bromocryptine (CB-154) inhibited total tumor area to 30 +/- 7% of the original volume. Combination of the two drugs, on the other hand, caused further inhibition to 10 +/- 5% of the pretreatment tumor area. The most striking effect of combination of the two drugs is a doubling of complete responses (no detectable tumor) from 30% when either drug was used alone to 60% in animals treated with the combination therapy. Both estradiol and progesterone receptors were further decreased when MPA was added to CB-154. The present data demonstrate that combination of the synthetic progestin MPA and the inhibitor of prolactin secrection CB-154 exerts maximal inhibitory effects on the growth of the DMBA-induced mammary tumor, the most widely used in vivo model of human breast cancer.
Dauvois
S
S
MRC Group in Molecular Endocrinology, Laval University Medical Center, Quebec, Canada.
Spinola
P G
PG
Labrie
F
F
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001971:Bromocriptine / Q000008:administration & dosage; D004357:Drug Synergism; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000032:analysis / Q000139:chemically induced / Q000188:drug therapy*; D008525:Medroxyprogesterone / Q000008:administration & dosage / Q000031:analogs & derivatives; D017258:Medroxyprogesterone Acetate; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D001971:Bromocriptine; D015127:9,10-Dimethyl-1,2-benzanthracene; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone