Inhibitory effect of luteinising hormone-releasing hormone analogues on human endometrial cancer in vitro Ivo Noci a, * , Marcella Coronnello b , Patrizia Borri a , Elena Borrani a , Massimo Giachi a , Orlando Chief® a , Mauro Marchionni a , Milena Paglierani c , Anna Maria Buccoliero c , Alessia Cherubini d , Annarosa Arcangeli d , Enrico Mini b , Gianluigi Taddei c a Department of Obstetrics and Gynecology, University of Florence, viale Morgagni 85, 50134 Florence, Italy b Department of Preclinical and Clinical Pharmacology, University of Florence, viale Pieraccini 6, 50134 Florence, Italy c Department of Human Pathology and Oncology, University of Florence, viale Morgagni 85, 50134 Florence, Italy d Department of Experimental Pathology and Oncology, University of Florence, viale Morgagni 85, 50134 Florence, Italy Received 12 July 1999; received in revised form 13 October 1999; accepted 13 October 1999 Abstract We studied the effects of luteinising hormone-releasing hormone (LHRH) agonist leuproreline (1 mM for 96 h) and LHRH antagonist cetrorelix on the cell growth of primary cultures from nine human endometrial cancers using the sulphorhodamine colorimetric test. Histological examinations and reverse transcription and polymerase chain reaction ampli®cation (RT±PCR) for LHRH receptors were also performed. The endometrial cancers examined had a medium to high degree of proliferative activity and a low degree of apoptotic power; furthermore, they expressed the LHRH receptor RNA variably, detectable in 71% of cases. The addition of leuproreline or cetrorelix to cell cultures inhibited growth in a statistically signi®cant way compared to untreated control cells; nevertheless, the percentage of cell growth inhibition obtained was very variable. These data suggest that LHRH analogues can exert differential inhibitory effects on the growth of endometrial cancer, which seems to be independent of the expression of speci®c LHRH receptors. q 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Endometrial cancer; LHRH analogue; Primary culture 1. Introduction Luteinising hormone-releasing hormone (LHRH) analogues (LHRH-a) affect the growth of sex-ster- oid-dependent tumours such as breast and prostate cancers by inhibiting gonadotropin secretion from the pituitary gland with the consequent decreased production of sex-steroids by the ovary and testis, respectively. Recent in vitro evidence suggests that LHRH-a can also exert direct inhibitory effects on the growth of prostatic, breast and ovarian carcino- mas, which are different from the indirect steroid hormone-related effects. These in vitro antiprolifera- tive effects have been associated with the presence of speci®c binding sites and receptor expression [1±4]. Endometrial cancer is the most common malig- nancy of the female genital tract and is currently the fourth most common malignancy in women [5]. The prognosis for most patients affected by endometrial cancer is relatively good, with an overall 5-year survi- val rate of 80±85%; however, the number of reported cancer deaths related to this disease is increasing [6]. The standard management of endometrial cancer is Cancer Letters 150 (2000) 71±78 0304-3835/00/$ - see front matter q 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S0304-3835(99)00374-2 www.elsevier.com/locate/canlet * Corresponding author. Tel.: 139-55-422-3328; fax: 139-55- 434-330. E-mail address: ginost@cesit1.uni®.it (I. Noci)