Antitumor effects of somatostatin

Abstract

SummarySince its discovery three decades ago as an inhibitor of GH release from the pituitary gland, somatostatin has attracted much attention because of its functional role in the regulation of a wide variety of physiological functions in the brain, pituitary, pancreas, gastrointestinal tract, adrenals, thyroid, kidney and immune system. In addition to its negative role in the control of endocrine and exocrine secretions, somatostatin and analogs also exert inhibitory effects on the proliferation and survival of normal and tumor cells. Over the past 15 years, studies have begun to reveal some of the molecular mechanisms underlying the antitumor activity of somatostatin. This review covers the present knowledge in the antitumor effect of somatostatin and analogs and discusses the perspectives of novel clinical strategies based on somatostatin receptor sst2 gene transfer therapy.

Contribution of HIF-1α in 4E-BP1 Gene Expression

“…This model has been chosen because in most human pancreatic tumors and derived cell lines, sst2 expression is dramatically decreased as compared with normal pancreas (16). As sst2 normally triggers antiproliferative signals (17), its absence leads to uncontrolled cell proliferation. We have however shown that sst2 reexpression conversely limits the proliferation of pancreatic cancer cells, likely via the induction of 4E-BP1 protein and the restoration of contact inhibition (18).…”

Octreotide enhances the sensitivity of the SKOV3/DDP ovarian cancer cell line to cisplatin chemotherapy in vitro

“…SST is a cyclic polypeptide hormone, which is located in most human organs and tissues. It functions in the inhibition of hormone secretion, regulation of neural transmission and cell proliferation (2,3). Natural SST is limited in clinical applications because of its low selectivity and short half-life.…”

“…Recently, the inhibitory effects of SST and SSTA on cancer cells have attracted the attention of researchers (9). A body of studies have reported that SST and SSTA inhibit the growth of several non-neuroendocrine tumors (3,(10)(11)(12), and it is known that the functions of SST and SSTA are mediated by the SSTR (13). SSTR2, followed by SSTR1, 3 and 4, are widely expressed in tumor tissues.…”

“…The somatostatin analogue (SSTA) shares similar physiological activities with natural SST, but has more powerful effects and a longer half-life. It has been shown that SSTA not only inhibits the proliferation of neuroendocrine tumors in vitro, but also inhibits solid tumor growth in vivo (2)(3)(4). The specific somatostatin receptor (SSTR), with five subtypes, mediates the functions of SSTA.…”

“…More than two receptor subtypes are easily detected in most types of tumor tissue, particularly SSTR2. SSTR2 mediates the inhibition of cell proliferation via the activation of Ras-, Rapl-and B-Raf-dependent extracellular signal-regulated kinase 2 (Erk2) (3)(4)(5). It has been reported the SSTR is expressed in ovarian cancer cells (6,7), suggesting that SSTA may be involved in ovarian cancer.…”