Endocrine Abstracts (2004) 7 P104

A somatostatin analogue and octreotide exert anti-proliferative effects on colonic cancer cells

S Khalaf1, F Bailey1, D Davies3, BW Ogunkolade1, P Kelly1, K McCarthy4, CA Laban4, SA Bustin2 & PJ Jenkins1


1Department of Endocrinology, Barts and The London, Queen Mary College, London, UK; 2Department. of Academic Surgery, Barts and The London, Queen Mary College, London, UK; 3The ICRF Unit, Lincoln's Inn, London, UK; 4Breast Unit, Barts and The London, Queen Mary College, London, UK


Introduction: Somatostatin and its analogues (SSA) have been reported to have anti-proliferative effects. We have recently demonstrated expression of all 5 somatostatin receptor sub-types in normal and malignant colonic tissue. SOM-230 (Novartis) is a novel SSA that has a wider binding affinity to somatostatin receptors compared to octreotide (OCT). Its effects on proliferation of colonic cancer cells are unknown.

Aims: To determine the effects of SOM-230 and OCT on proliferation and apoptosis of colorectal cancer cells.

Methods: HT29 cells, a human colorectal cancer cell line, were cultured for 24, 48 and 72hrs in serum free media with 10-12 -10-6 M of SOM-230 or OCT.

Assessment was made of (i) proliferation by the colorimetric MTS assay and direct cell counting using trypan blue and (ii) apoptosis by FACS analysis.

Results: 10-12 and 10-11M SOM-230 exerted significant anti-proliferative activity at 24hrs (mean cell number compared to media only: 83% and 87% respectively: P<0.001 and < 0.02). 10-8+ 10-7M SOM-230 also caused inhibition at both 24hrs (mean: 78% and 84% respectively, P < 0.001) and 48hrs (mean: 63% and 77% P < 0.0001).

OCT caused similar inhibitory effects at 24hrs: 10-12 and 10-11M (mean: 67% and 65% P < 0.02 and 0.001; 10-8 and 10-7M (mean: 65% and 63% P < 0.0001.These inhibitory effects by either compound were not accompanied by any increase in the population of apoptotic cells.

Conclusion: The SSAs, SOM-230 and OCT exert anti-proliferative effects on colonic cancer cells but do not induce apoptosis. The mechanisms responsible for this cytostatic effect remain to be determined

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