mdl-100907 and Prostatic-Neoplasms

Overexpression of receptors to neuroendocrine (NE) cell products has been suggested to contribute to development of hormone-refractory prostate cancer (HRPC). In this study, we evaluated the expression of 5-HTR2B and 5-HTR4 in HRPC, and the effects of their antagonist on PC cell line growth.. Proteins and mRNA expression was determined by immunohistochemistry, western blot and RT-PCR. Growth inhibition of PC cell lines was determined in vitro using ELISA-BrdU proliferation assay and cell cycle was evaluated by flow cytometry.. Immunostaining of 5-HTR2B was observed in low-grade and high-grade tumours, PIN and BPH cells, and in vascular endothelial cells, whereas 5-HTR4 was found predominantly in high-grade tumours. This result was confirmed by western blot analysis. At the mRNA level, 5-HTR4 mRNA was expressed in DU145 and LNCaP cells. Antagonists to both receptor subtypes inhibited proliferation of PC cells in a dose-dependent manner.. The present result indicate that 5-HTRs are present at various tumour stages and that antagonists to these receptors can inhibit the proliferative activity of androgen-independent PC cell lines.

Topics: Biomarkers, Tumor; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Humans; Immunohistochemistry; In Vitro Techniques; Male; Prostatic Neoplasms; Receptor, Serotonin, 5-HT2B; Receptors, Serotonin, 5-HT4; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Serotonin 5-HT2 Receptor Antagonists; Serotonin 5-HT4 Receptor Antagonists; Serotonin Antagonists