The direct effect of octreatide, galanin and serotonin on human colon cancer cells
Department of Medicine, University Hospital, Umeå, Sweden
Aim: To investigate the effect of octreotide, galanin and serotonin on a human colon cancer cells at different concentrations, with different combinations and at different time intervals. Methods: The human colon cancer cell line (SW 620) was exposed to mono-, double and triple combinations of octreotide, galanin and serotonin with doses 0.2, 0.1 and 0.05 µg/ml and were observed after 3, 6, 12, 24 and 48 h. MTT-assay was used to determine the number of viable cells. Proliferation and apoptosis were detected by immunocytochemistry using avidin-biotin complex (ABC) method. The antibodies used were anti- Ki-67, anti-poly (ADP-ribose) polymerase "PARP" and anti-Bcl-x. Proliferative and apoptotic indexes were determined by computerized image analysis. Results: Almost all the mono and double treatment of the bioactive substances decrease the number of the viable cells. With triple treatment, however, this decrease was greater and could be seen at all the observation times. The effect on proliferation varied from none, an enhancing or inhibiting action, depending on the dose, combination and observation time. The effect of mono- or double exposure to the bioactive gut substances varies, depending on the concentration, combination and observation time. Triple combination at the effective dose increased the apoptotic index by the 2 markers used, and appeared after 6 h and extended up to 48 h. Conclusions: The reduction in the number of viable cancer cells observed was greater and occurred earlier than the increase in apoptosis and observed when the bioactive substances used alone or in combinations and at different concentrations. It is reasonable therefore to conclude that other mechanisms than apoptosis are involved which result in inhibiting cancer cell respiration. It is possible that some of the in vivo dramatic changes seen earlier after triple treatment with octreotide, galanin and serotonin can be due to a direct effect of these substances on cancer cells.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 991 (Synergistic therapies).