Suppression of the growth of the androgen-insensitive R3327 HI rat prostatic carcinoma by combined estrogen and antiprogestin treatment.
The antiprogestin RU486 has been shown to inhibit the growth of a number of tumor cell lines and solid tumors which contain significant concentrations of progesterone receptor (PgR). It has been suggested that growth suppression may be due to a PgR-mediated cytotoxic effect. The R3327 HI prostatic carcinoma of the rat is considered to be a model for human prostatic carcinoma which has become resistant to androgen deprivation therapy. Since it is possible to induce high concentrations of PgR in this tumor with estrogen, it was of interest to investigate the possibility that RU486 could suppress its growth. Growth was assessed by tumor diameter, [3H]thymidine uptake and histopathological appearance after 2 or 8 weeks treatment with RU486 alone, diethylstilbestrol (DES) alone, and combined RU + DES treatment as compared with control animals. Tumor growth was not affected significantly by DES treatment alone. RU486 treatment alone suppressed PgR content and resulted in only insignificant inhibition of growth. However, when significant PgR concentrations were maintained by combined treatment with DES, RU486 significantly suppressed tumor growth (0.01 less than P less than 0.05 vs controls). This was accompanied by atrophy of the glandular epithelium. The results support the hypothesis that growth suppression may be brought about by a PgR-mediated mechanism. The data suggest that it may be possible to treat androgen-insensitive prostatic carcinoma by a new form of hormonal treatment.
Mobbs
B G
BG
Department of Surgery, University of Toronto, Ontario, Canada.
Johnson
I E
IE
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D011980:Receptors, Progesterone; D014316:Tritium; D015735:Mifepristone; D004054:Diethylstilbestrol; D013936:Thymidine