Comparison between triple therapy with octreotide, galanin and serotonin vs. irinotecan or oxaliplatin in combination with 5-fluorouracil/leukovorin in human colon cancer.
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.
El-Salhy
M
M
Division of Gastroenterology and Hepatology, Endocrine-Gastroenterology Clinic, University Hospital, SE-581 85 Linköping, Sweden. magdy.el-salhy@imk.liu.se
Hilding
L
L
Royson
H
H
Tjomsland
V
V
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004815:Epidermal Growth Factor / Q000032:analysis; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D019004:Galanin / Q000008:administration & dosage; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D015282:Octreotide / Q000008:administration & dosage; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012701:Serotonin / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D009944:Organoplatinum Compounds; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; D012701:Serotonin; D004815:Epidermal Growth Factor; D000077146:Irinotecan; D019004:Galanin; D011065:Poly(ADP-ribose) Polymerases; D002955:Leucovorin; D015282:Octreotide; D005472:Fluorouracil; D002166:Camptothecin