The dopamine-somatostatin chimeric compound BIM-23A760 exerts antiproliferative and cytotoxic effects in human non-functioning pituitary tumors by activating ERK1/2 and p38 pathways

作者：Peverelli Erika; Olgiati Luca; Locatelli Marco; Magni Paolo; Fustini Marco Faustini; Frank Giorgio; Mantovani Giovanna; Beck Peccoz Paolo; Spada Anna; Lania Andrea^*

来源：Cancer Letters, 2010, 288(2): 170-176.

DOI：10.1016/j.canlet.2009.06.034

• Pituitary adenoma
• Dopamine receptor
• Somatostatin receptor
• Cell proliferation
• Apoptosis
• Chimera

The Study investigated the effects of the dopamine-somatostatin chimeric compound BIM-23A760 on cell proliferation and apoptosis in cultured cells from human non-functioning pituitary tumors (NFPTs). Both BIM-23A760 and the dopaminergic agonist BIM-53097 induced a significant inhibition of cell proliferation associated with increased p27 expression, together with a significant increase in caspase-3 activity. Conversely, null or marginal effects were elicited by somatostatin analogs. Moreover, BIM-23A760 and BIM-53097 induced ERK1/2 and p38 phosphorylation and the blockade of these pathways prevented both the antiproliferative and the pro-apoptotic effects of these drugs. In conclusions the chimeric compound BIM-23A760 is able to exert cytostatic and cytotoxic effects in NFPTs, these phenomena being mainly mediated by DR2D and involving ERK1/2 and p38 pathways activation.

• 出版日期2010-2-28