Abstract
Peptide hormone somatostatin and its receptors have a wide range of physiological functions and play a role in the treatment of numerous human diseases, including colorectal cancer. Octreotide, a synthetic somatostatin-analog peptide, inhibits growth of colonic cancer cells primarily by binding to G-protein coupled receptors and elicits cellular responses through second-messenger systems. Insulin also initiates mitogenic signals in certain cell types. The objective of the present study was to explore the effects of octreotide with or without insulin treatment, on Caco-2 and HT-29 human colon-cancer cell proliferation and to correlate their effects with the activation of telomerase reverse transcriptase (hTERT). The involvement of protein tyrosine phosphatases in the regulation of the anti-proliferative effect of octreotide was also evaluated. Sodium orthovanadate was used to reverse the anti- proliferative effect of octreotide. Telomerase activity was determined for each time point under octreotide and/or insulin treatment. Elevated expression of sst1, sst2 and sst5 was confirmed in both cell lines by RT-PCR. Immunocytochemistry detected sst1, sst2A, sst2B, sst3, sst4 and sst5 protein expression in the membranes of both cell lines. Octreotide inhibited the proliferation of Caco-2 and HT-29 cells in a time and dose-dependent manner. Insulin exerted proliferative effects in Caco-2 cells and octreotide reversed its effect in both cell lines. Sodium orthovanadate suppressed the anti-proliferative effect of octreotide both in Caco-2 and HT-29 cells. Telomerase activity was significantly reduced when Caco-2 cells were exposed to octreotide, under serum-free cultured medium. On the other hand, telomerase attenuation after octreotide treatment could not counteract the actions of insulin on both cells. Our data indicate that the use of octreotide could provide a possible therapeutic approach to the management of certain patients who suffer from colon cancer.
Highlights
Colorectal cancer is one of the most common malignancies encountered in the western world and the third most common cause of cancer-related mortality
We investigated the involvement of protein tyrosine phosphatases (PTPs) and telomerase activity in cellular proliferation
While long-acting synthetic somatostatin analogues target the somatostatin receptors, they differ in their binding affinity to these receptors [13], Somatostatin binds with high affinity to all somatostatin receptors, while octreotide is a preferential sst2 ligand, which targets the high levels of somatostatin receptor subtype 2 expressed in colon cancers [13]
Summary
Colorectal cancer is one of the most common malignancies encountered in the western world and the third most common cause of cancer-related mortality. Somatostatin was originally described as a natural growth-hormone-release inhibiting factor but it was later proved to have many metabolic and immunological effects through binding to five somatostatin receptors (ssts) [1, 2]. These receptors are G-protein coupled receptors and elicit cellular responses through second-messenger systems. These include both “direct” mechanisms and “indirect” mechanisms that might be the result of reduced or inhibited secretion of growth-promoting hormones and growth factors that stimulate the growth of various types of malignancies [3, 4]. Insulin is a peptide hormone produced by the beta pancreatic cells, and it has been shown to initiate mitogenic signals in certain cell types, acting as a trophic factor in tumor cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
