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Human colon cancer cells were injected sub-cutaneously into 30 nude mice. After 8 days, the animals were divided into 3 equal groups. The first and second groups received an i.p. injection with 5-fluorouracil/leukovorin (5-FU/LV) for 5 days (20 mg and 10 mg/kg body weight respectively). On the first day of 5-FU/LV treatment, the first group received an i.p. injection of irinotecan (2.5 mg/kg body weight), and the second group received an i.p. injection with oxaliplatin (1 mg/kg body weight). The third group were injected i.p. with 100 microl saline solution containing octreotide, galanin and serotonin. Injections were given 3 times daily for 5 days with a total dose of 150 microg/kg body weight/day. Three days after the treatment, the animals were sacrificed. Whereas the animals treated with triple therapy held a stable body weight, animals treated with 5-FU/LV-irinotecan and 5-FU/LV-oxaliplatin had gradual weight loss, which amounted to approximately 25% of their body weight at the end of the experiment. Moreover, 2 mice in the group treated with 5-FU/LV-irinotecan died, most probably due to side effects. There was no statistically significant difference between the 3 groups regarding tumour proliferation, apoptosis, blood vessel density, EGF- and VEGF-expression. Treatment with triple therapy using octreotide, galanin and serotonin appear to be comparable to 5-FU/LV in combination with irinotecan and oxaliplatin. However, triple therapy seems to have a better safety profile.

Human colon cancer cells were injected subcutaneous in nude mice. After 8 days the animals were divided in two groups, the first group received triple therapy with octreotide, galanin and serotonin (40 microg/kg body weight/day) through an ALZET osmotic pump implanted intraperitoneally (i.p.) for 14 days, followed by 5 days of subcutaneous injections (200 microg/kg body weight/ day). The second group was injected i.p. for 5 days with 5-fluorouracil/leukovorin (5-FU/LV) at concentrations of 4 mg and 2 mg/kg body weight, respectively. After 9 days without any treatment, the mice received i.p. injection with 5-FU/LV (20 mg and 10 mg/kg body weight/day, respectively) for another 5 days. The volume and weight of the tumours were measured at the end of the experiment. Apoptosis, proliferation, blood vessels, epidermal growth factor (EGF) and vascular endothelial cell growth factor (VEGF) were detected with immunocytochemistry. Apoptosis was also detected using the TUNEL-method. Quantification was performed using computed image analysis. There was no statistical significance between tumours treated with 5-FU/LV or triple therapy regarding the volume and weights of the tumours, apoptotic, proliferation, VEGF indces and the density of tumour blood vessels. The EGF labelling index was, however significantly lower in the tumours treated with triple therapy than those treated with 5-FU/LV. In conclusion, treatment with triple therapy using octreotide, galanin and serotonin appear to be comparable with 5-FU/LV that is the standard chemotherapeutic agent for colorectal cancer.

Human colon cancer cells were implanted subcutaneously into nude mice. After 12 days, the animals were divided into two groups. The first group received 40 microg/kg body weight of octreotide, galanin and serotonin via an intraperitoneally implanted pump. The second group received sterile saline only. Treatment lasted for 14 days. The volume and weight of the tumours in treated mice tended to decrease, though not with statistical significance. The proliferation index and the number of tumour blood vessels was significantly reduced in the mice given triple therapy. The apoptotic index, as detected by TUNEL method and monoclonal anti-poly (ADP-ribose) polymerase, was significantly higher in the treated mice. Though the results of this investigation are promising, it is uncertain as to what use the present findings may imply for the treatment of patients with colorectal cancer.

Human colon cancer cells (SW 620) were implanted under the capsule of the left liver lobe of female nude (C57BL/6JBom-nu) mice. After 7 days, relaparatomy was performed and an ALZET osmotic pump was implanted intraperitoneally and left in situ for 14 days. The mice were divided into 2 groups, 10 in each. The first group received 40 micro g/kg body weight of octreotide, galanin and serotonin, and the second group received sterile saline. The number of metastases in the liver, and to the intra-abdominal lymph nodes was significantly greater in the controls. The incidence of metastases to the peritoneal cavity was lower in the treated animals (though not statistically significantly). Tumour volume, wet weight, proliferation index and number of tumour blood vessels decreased significantly in the treated animals. The apoptotic index was significantly higher in the treated mice. The decrease in the volume and weight of tumours following the triple therapy seemed to be caused by low proliferation, and increased apoptosis, and reduced vascularization of the tumours. The low invasion of cancer cells observed following this treatment could have been due to the low tumour burden, and to the reduced number of the blood and lymph vessels.

Human colon cancer cells were implanted s.c. in nude mice. After 6 days, the mice were divided into four groups, 10 in each. During the first 5 days, the first and second groups were injected i.p. with leucovorin (LV)/5-fluorouracil (FU), and the third and fourth groups with sterile saline solution. During the subsequent 14 days, groups 1 and 4 received continuous i.p. infusion with sterile saline solution, while groups 2 and 3 received octreotide, galanin and serotonin via an implanted osmotic pump. Tumour volumes diminished significantly in mice treated with both LV/FU and LV/FU-triple therapy, as compared with controls. Both volume and weight of the tumours in mice given LV/FU-triple therapy were less than in those received LV/FU. The volume and weight of the tumours in animals treated with triple therapy was reduced as compared with controls, though not statistically significantly. The proliferation index, and the number of tumour blood vessels were both reduced, while the apoptotic index was increased in the mice treated with both LV/FU-triple therapy, and with triple therapy only as compared with LV/FU-treated mice. The present study has shown that the anti-tumour efficacy and therapeutic efficacy of triple therapy with octreotide, galanin and serotonin is equivalent to LV/FU and that sequential treatment with both could be beneficial.