Effects of triple therapy with octreotide, galanin and serotonin on a human colon cancer cell line implanted in mice: comparison between different routes of administration.
A human colon cancer cell line was implanted subcutaneously in nude mice. After 7 days, the animals were divided into four groups. The first group received an intraperitoneal (i.p.) continuous infusion by an osmotic pump, the second was given i.p. bolus injections, the third received continuous subcutaneous (s.c.) infusion by an osmotic pump and the fourth group was given bolus s.c. injections. Each group was divided into 2 subgroups. The first subgroup received triple treatment with octreotide, galanin, and serotonin, 40 microg/kg body weight/day of each. The second subgroup was given sterile saline solution. Treatment lasted for 14 days. The volume and wet weight of the tumours in all treated groups tended to decrease, but was statistically significant only in the group with continuous i.p. infusion. The number of viable cells tended to decrease in all the treated groups, but was not statistically significant. Proliferation index was significantly reduced in mice given triple therapy i.p. as bolus injection and as continuous infusion, as compared with their respective controls. The apoptotic index increased significantly in mice receiving triple therapy as continuous i.p. infusion as revealed by both the TUNEL method and by poly (ADP-ribose) polymerase (PARP) expression. The number of tumour blood vessels was significantly reduced in the mice given triple therapy as continuous i.p. infusion, as compared with controls. There was no statistical difference between animals treated by different routes, regarding proliferation or apoptosis of the cancer cells, or the number or mean luminal area of tumour blood vessels. The present investigation showed that regardless of the route of administration, triple therapy with octreotide, galanin and serotonin generally reduced the volumes, weights, viable cells, vascularization and proliferation of the tumours, as well as inducing apoptosis. Continuous i.p. infusion appears, however, to be the most effective route of administration.
El-Salhy
M
M
Division of Gastroenterology and Hepatology, Institution of Molecular and Clinical Medicine, University Hospital, S-581 85 Linköping, Sweden. magdy.el-salhy@imk.liu.se
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D019004:Galanin / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D008819:Mice, Nude; D015282:Octreotide / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology*
D018931:Antineoplastic Agents, Hormonal; D016166:Free Radical Scavengers; D012701:Serotonin; D019004:Galanin; D015282:Octreotide