INHIBITION OF GROWTH OF ANDROGEN-INDEPENDENT DU-145 PROSTATE-CANCER IN-VIVO BY LUTEINIZING-HORMONE-RELEASING HORMONE ANTAGONIST CETRORELIX AND BOMBESIN ANTAGONISTS RC-3940-II AND RC-3950-II
A. Jungwirth et al., INHIBITION OF GROWTH OF ANDROGEN-INDEPENDENT DU-145 PROSTATE-CANCER IN-VIVO BY LUTEINIZING-HORMONE-RELEASING HORMONE ANTAGONIST CETRORELIX AND BOMBESIN ANTAGONISTS RC-3940-II AND RC-3950-II, European journal of cancer, 33(7), 1997, pp. 1141-1148
The aim of this study was to test the antagonist of LH-RH (CetroreLix)
, agonist [D-Trp(6)]LH-RH (triptorelin) and new bombesin antagonists R
C-3940-II and RC-3950-II for their effect on the growth of an androgen
-independent prostate cancer cell line, DU-145, xenografted into nude
mice. Xenografts were grown in male nude mice, and after 4 weeks, the
animals were treated either with saline (control) or with one of the a
nalogues. One group of mice was given a combination of Cetrorelix and
RC-3950-II. Treatment was given for 4 weeks. Tumour and body weights,
and tumour volumes were measured. At sacrifice, tumours were dissected
for histological examination and receptor studies. Serum was collecte
d for measurement of hormone levels. The final tumour volume in contro
l animals injected with saline was 577 +/- 155 mm(3) and that of anima
ls treated with Cetrorelix only 121.4 +/- 45 mm(3) (P < 0.01). Bombesi
n antagonists RC-3940-II and RC-3950-II also significantly reduced DU-
145 tumour volume in nude mice to 84.9 +/- 19.9 and 96.8 +/- 28 mm(3),
respectively. Agonist [D-Trp(6)]LH-RH did not significantly inhibit t
umour growth. Serum levels of LH were decreased to 0.08 +/- 0.02 ng/ml
(P < 0.05) in the Cetrorelix treated group as compared to 1.02 +/- 0.
1 ng/ml for the controls, and testosterone levels were reduced to cast
ration levels (0.01 +/- 0.01 ng/ml). Specific receptors for EGF and LH
-RH in DU-145 tumours were significantly downregulated after treatment
with Cetrorelix, RC-3940-II and RC-3950-II. Although LH-RH could be a
local regulator of growth of prostate cancer, the fall in LH-RH recep
tors is not fully understood and the inhibitory effects of Cetrorelix
and bombesin antagonists on DU-145 tumour growth might be attributed a
t least in part to a downregulation of EHF receptors. Since Cetrorelix
and bombesin antagonists inhibit growth of androgen-independent DU-14
5 prostate cancers, these compounds could be considered for the therap
y of advanced prostate cancer in men, especially after relapse. (C) 19
97 Elsevier Science Ltd.