Effects of octreotide and insulin on colon cancer cellular proliferation and correlation with hTERT activity.
Georgios D. Ayiomamitis1,2, George Notas1,3, Apostolos Zaravinos4,5, Ioannis Drygiannakis1, Maria Georgiadou1, Ourania Sfakianaki1, Niki Mastrodimou6, Kyriaki Thermos6, Elias Kouroumalis1,7
1 Laboratory of Gastroenterology, School of Medicine, University of Crete, Heraklion, Greece.
2 2nd Department of Surgery, Tzaneion General Hospital, Piraeus, Greece.
3 Laboratory of Experimental Endocrinology, School of Medicine, University of Crete, Heraklion, Greece.
4 Laboratory of Clinical Virology, School of Medicine, University of Crete, Heraklion, Greece.
5 Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
6 Laboratory of Pharmacology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
7 Department of Gastroenterology and Hepatology, School of Medicine, University of Crete, Heraklion, Greece.
Correspondence:
Elias Kouroumalis, email:
Keywords: Octreotide, insulin, colorectal cancer, hTERT activity, protein tyrosine phosphatases, sodium orthovanadate.
Received: June 1, 2014 Accepted: June 28, 2014 Published: June 30, 2014
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.
