Somatostatin (SRIF) has been demonstrated to inhibit in vitro proliferation of normal and transformed cells via SRIF receptors (ssts). Moreover, like other neuroendocrine molecules, SRIF and ssts may play a significant role in the progression and neuroendocrine differentiation of human prostate cancer (PCa). However, conflicting results have been reported in the literature on ssts heterogeneity and specific cell localization in PCa. In the present study, using the human androgen-independent PCa cell lines DU-145 and PC-3, we investigated: (1) ssts gene and protein expression and (2) the effects of SRIF agonists on cell proliferation. DU-145 and PC-3 cells expressed all five isoforms codenamed sst1-5 and among them sst2 and sst5 were highly expressed (RT-qPCR). Western blot analysis of cell membrane extracts showed that in these cells all ssts were present, except sst2. Dose-response studies, evaluated by 5-bromo-2’-deoxyuridine incorporation, were performed at 48 h with a dose range from 10-10 to 10-6 M. In DU-145 cells, BIM-23296 (sst1) was significantly more potent in inhibiting cell proliferation (-30 %) than BIM-23206 (sst5) and BIM-23244 (sst2/sst5) (both -15%). The same rate of cell growth inhibition has been showed in PC-3 cells, where BIM-23296 (sst1) and BIM-23206 (sst5) resulted the more potent compound tested (both -35%). BIM-23704 (sst1/sst2) was not able to affect cell proliferation in both cell lines. In conclusion, DU-145 and PC-3 cells may represent a useful PCa model for studying ssts trafficking/regulation, intracellular subtype-linked signalling, and validate new SRIF analogs with different receptor affinities in PCa treatment.

EFFECTS OF SOMATOSTATIN ANALOGS ON CELL PROLIFERATION OF HUMAN ANDROGEN-INDEPENDENT PROSTATE CANCER CELL LINES / M. Ruscica, M. Arvigo, L. Steffani, L. Passafaro, M.A. Busolo, P. Ameri, F. Minuto, M. Culler, M. Motta, D. Ferone, P. Magni. ((Intervento presentato al 35. convegno Congresso Nazionale della Società Italiana di Endocrinologia tenutosi a Montesilvano nel 2011.

EFFECTS OF SOMATOSTATIN ANALOGS ON CELL PROLIFERATION OF HUMAN ANDROGEN-INDEPENDENT PROSTATE CANCER CELL LINES

M. Ruscica
Primo
;
L. Steffani;L. Passafaro;M. Motta;P. Magni
Ultimo
2011-05

Abstract

Somatostatin (SRIF) has been demonstrated to inhibit in vitro proliferation of normal and transformed cells via SRIF receptors (ssts). Moreover, like other neuroendocrine molecules, SRIF and ssts may play a significant role in the progression and neuroendocrine differentiation of human prostate cancer (PCa). However, conflicting results have been reported in the literature on ssts heterogeneity and specific cell localization in PCa. In the present study, using the human androgen-independent PCa cell lines DU-145 and PC-3, we investigated: (1) ssts gene and protein expression and (2) the effects of SRIF agonists on cell proliferation. DU-145 and PC-3 cells expressed all five isoforms codenamed sst1-5 and among them sst2 and sst5 were highly expressed (RT-qPCR). Western blot analysis of cell membrane extracts showed that in these cells all ssts were present, except sst2. Dose-response studies, evaluated by 5-bromo-2’-deoxyuridine incorporation, were performed at 48 h with a dose range from 10-10 to 10-6 M. In DU-145 cells, BIM-23296 (sst1) was significantly more potent in inhibiting cell proliferation (-30 %) than BIM-23206 (sst5) and BIM-23244 (sst2/sst5) (both -15%). The same rate of cell growth inhibition has been showed in PC-3 cells, where BIM-23296 (sst1) and BIM-23206 (sst5) resulted the more potent compound tested (both -35%). BIM-23704 (sst1/sst2) was not able to affect cell proliferation in both cell lines. In conclusion, DU-145 and PC-3 cells may represent a useful PCa model for studying ssts trafficking/regulation, intracellular subtype-linked signalling, and validate new SRIF analogs with different receptor affinities in PCa treatment.
somatostatin
Settore MED/13 - Endocrinologia
Settore MED/05 - Patologia Clinica
Settore BIO/13 - Biologia Applicata
Settore BIO/09 - Fisiologia
EFFECTS OF SOMATOSTATIN ANALOGS ON CELL PROLIFERATION OF HUMAN ANDROGEN-INDEPENDENT PROSTATE CANCER CELL LINES / M. Ruscica, M. Arvigo, L. Steffani, L. Passafaro, M.A. Busolo, P. Ameri, F. Minuto, M. Culler, M. Motta, D. Ferone, P. Magni. ((Intervento presentato al 35. convegno Congresso Nazionale della Società Italiana di Endocrinologia tenutosi a Montesilvano nel 2011.
Conference Object
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/159304
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact