No supra-additive effects of goserelin and radiotherapy on clonogenic survival of prostate carcinoma cells in vitro.
BACKGROUND
Oncological results of radiotherapy for locally advanced prostate cancer (PC) are significantly improved by simultaneous application of LHRH analoga (e.g. goserelin). As 85% of PC express LHRH receptors, we investigated the interaction of goserelin incubation with radiotherapy under androgen-deprived conditions in vitro.


METHODS
LNCaP and PC-3 cells were stained for LHRH receptors. Downstream the LHRH receptor, changes in protein expression of c-fos, phosphorylated p38 and phosphorylated ERK1/2 were analyzed by means of Western blotting after incubation with goserelin and irradiation with 4 Gy. Both cell lines were incubated with different concentrations of goserelin in hormone-free medium. 12 h later cells were irradiated (0 - 4 Gy) and after 12 h goserelin was withdrawn. Endpoints were clonogenic survival and cell viability (12 h, 36 h and 60 h after irradiation).


RESULTS
Both tested cell lines expressed LHRH-receptors. Changes in protein expression demonstrated the functional activity of goserelin in the tested cell lines. Neither in LNCaP nor in PC-3 any significant effects of additional goserelin incubation on clonogenic survival or cell viability for all tested concentrations in comparison to radiation alone were seen.


CONCLUSIONS
The clinically observed increase in tumor control after combination of goserelin with radiotherapy in PC cannot be attributed to an increase in radiosensitivity of PC cells by goserelin in vitro.
Hermann
Robert M
RM
Department of Radiotherapy, University hospital, Göttingen, Germany. ro.hermann@t-online.de
Schwarten
Dag
D
Fister
Stefanie
S
Grundker
Carsten
C
Rave-Frank
Margret
M
Nitsche
Mirko
M
Hille
Andrea
A
Thelen
Paul
P
Schmidberger
Heinz
H
Christiansen
Hans
H
Lancet. 2002 Jul 13;360(9327):103-6
12126818
Int J Radiat Oncol Biol Phys. 2005 Nov 15;63(4):1221-7
16253776
Prostate. 2005 Dec 1;65(4):331-40
16015611
Int J Radiat Oncol Biol Phys. 2000 Jan 1;46(1):153-8
10656387
Urol Res. 1999 Oct;27(5):357-61
10550524
J Cell Biochem. 2002;85(3):470-81
11967986
Steroids. 1996 Apr;61(4):222-5
8733005
N Engl J Med. 1997 Jul 31;337(5):295-300
9233866
Clin Cancer Res. 2002 Apr;8(4):1251-7
11948140
Hinyokika Kiyo. 1999 Aug;45(8):543-6
10500960
J Biol Chem. 2005 Jun 17;280(24):23262-72
15837784
Int J Radiat Oncol Biol Phys. 1976 Nov-Dec;1(11-12):1043-8
791909
J Urol. 2000 Feb;163(2):623-9
10647698
Prostate. 1997 Aug 1;32(3):164-72
9254895
Int J Urol. 2002 Jun;9(6):322-8; discussion 328
12269247
Int J Radiat Oncol Biol Phys. 1977 Sep-Oct;2(9-10):873-83
412817
Int J Radiat Oncol Biol Phys. 2001 Aug 1;50(5):1243-52
11483335
Int J Radiat Oncol Biol Phys. 1997 Jul 15;38(5):1071-7
9276374
Mol Cell Endocrinol. 2006 Jun 27;252(1-2):184-90
16682115
Int J Radiat Oncol Biol Phys. 2001 Nov 15;51(4):1002-7
11704324
Cancer. 1979 Mar;43(3):1123-7
85478
Eur J Endocrinol. 2004 Jul;151(1):141-9
15248835
Cancer Res. 2007 Feb 15;67(4):1750-6
17308117
Int J Radiat Oncol Biol Phys. 2003 Sep 1;57(1):24-8
12909211
Cancer Res. 1994 Aug 1;54(15):4091-5
8033142
J Clin Endocrinol Metab. 1992 Jul;75(1):207-12
1320049
Eur J Endocrinol. 2004 Nov;151(5):619-28
15538941
J Urol. 1998 Jun;159(6):2030-4
9598512
Br J Urol. 1992 Sep;70(3):304-9
1422689