Triple therapy with octreotide, galanin and serotonin reduces the size and tumor blood vessels and increases apoptosis in a human colon carcinoma
Department of Medicine, University Hospital, Umeå, Sweden
Aim: To investigate the effect triple therapy with octreotide, galanin and serotonin on a human colon cancer. Methods: The human colon cancer cell line (SW 620) was implanted subcutaneously in female nude mice. After seven days, the animals were divided into 4 groups. All the groups received triple therapy with octreotide, galanin, and serotonin, 40 ug/kg body weight/day of each. They were administrated as a single subcutaneous injection in the first group, as a continuous subcutaneous infusion in the second group, as a single intraperitoneal injection in the third group and as a continuous intraperitoneal infusion in the last group. The treatment lasted for 14 days. The tumor volume and weight were measured at the end experiments. MTT-assay was used to determine the number of viable cells. Proliferation, apoptosis and tumor blood vessels were detected by immunocytochemistry using avidin-biotin complex (ABC) method. The antibodies used were anti- Ki-67, anti-poly (ADP-ribose) polymerase "PARP", anti-Bcl-x and CD31.Proliferative and apoptotic indexes as well as the number and luminal area of the tumor blood vessels were determined by computerized image analysis. Results: The volume and weight of the tumors were decreased in the group with continuous intraperitoneal infusion. The apoptotic index increased and the number and luminal area of the tumor blood vessels decreased in the group treated with continuous intraperitoneal infusion. There was no effect regarding the proliferation index Conclusions: Triple therapy with octreotide, galanin and serotonin was effective in reducing the volume and weight of a human colon carcinoma and that continuous intraperitoneal infusion is the most effective way of administration. The reduction in the tumor volume and weight may be caused the tumor ischemia and apoptosis of cancer cells. The ischemia of the cancer cells might be caused by the reduced the number and constriction of the tumor-feeding blood vessels.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 991 (Synergistic therapies).