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The Synergistic Effects of the Somatostatin Analog Pasireotide (SOM230) and Raf-1 Pathway Activation in Human Carcinoid Cancer Cells

Abstract:

Background: Gastrointestinal (GI) carcinoids are rare neuroendocrine (NE) tumors characterized by the production of bioactive hormones such as 5-hydroxytryptamine and chromogranin A. Besides surgery, there are limited curative and palliative treatments available. We have previously demonstrated that combined therapy with octreotide, a naturally occurring somatostatin analog which is effective in managing symptoms in patients with the malignant carcinoid syndrome, and Raf-1 pathway activation results in synergistic growth inhibition without synergistic effects on NE hormone production. In the present study, we investigate the synergistic effects of the recently developed long-acting somatostatin analog, pasireotide (SOM 230), and Raf-1 pathway activation. Methods: Human gastrointestinal carcinoid tumor cells stably transduced with an estradiol-inducible Raf-1 construct (BON-Raf) were treated with 1μM β …