Effects of tamoxifen, estradiol benzoate and medroxyprogesterone acetate on the growth of DMBA-induced rat mammary carcinoma.
The potential synergism of sequential combinations of tamoxifen (TMX) or estradiol benzoate (E2B) with medroxyprogesterone acetate (MPA) in inhibiting the growth of 7.12-dimethylbenz(a)anthracene(DMBA) - induced rat mammary tumors has been investigated. In addition, the effect of TMX and E2B on estrogen and progesterone receptors' (ERs and PgRs) synthesis has been evaluated in the attempt to elucidate possible mechanisms involved. Previous treatment both with TMX and E2B has been shown to strongly enhance the antitumor activity of MPA. A priming on PgR synthesis has been observed only after E2B administration, TMX producing a sharp decrease in PgR levels. It is concluded that, while the priming action exerted by E2B on PgRs might explain the potentiating effect shown by E2B on MPA activity, the synergism observed between TMX and MPA should be explained on an extrareceptorial basis, an induction on PgR synthesis by TMX not being evident at the dosage and priming time employed in this study.
Zanardi
S
S
De Menech
R
R
Pino
G
G
Guarneri
D
D
Dandolo
G
G
Sanguineti
M
M
Moro
M G
MG
Barbi
G P
GP
Paganuzzi
M
M
Boccardo
F
F
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004357:Drug Synergism; D004958:Estradiol / Q000008:administration & dosage; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D008525:Medroxyprogesterone / Q000008:administration & dosage / Q000031:analogs & derivatives; D017258:Medroxyprogesterone Acetate; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013629:Tamoxifen / Q000008:administration & dosage
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone