Impact of Octreotide and SOM-230 on liver metastasis and hepatic lipidperoxidation in ductal pancreatic adenocarcinoma in Syrian Hamster.
Octreotide is a somatostatin analogue binding on two receptor subtypes. In previous trials Octreotide showed inhibitory effects on tumour growth and liver metastasis in experimental pancreatic cancer. Thus we evaluated whether the new somatostatin analogue SOM-230 binding on 4 receptor subtypes has superior effects on carcinogenesis in pancreatic carcinoma. About 120 Syrian hamsters were randomised into six groups (n = 20): Gr.1: Aqua/Aqua, Gr.2: BOP/Aqua, Gr.3: Aqua/Octreotide, Gr.4: BOP/Octreotide, Gr.5: Aqua/SOM-230, Gr.6: BOP/SOM-230. Tumour groups 2,4,6 subcutaneously received 10 mg/kg body weight N-nitrosobis-2-oxopropylamin (BOP) weekly for 10 weeks, healthy control Gr.1,3,5 were given aqua. In the 17th week therapy started with Octreotide and SOM-230 for 16 weeks, after 32 weeks animals were sacrificed. Pancreas and liver were histopathologically analysed. Hepatic lipidperoxidation was determined by activities of antioxidative enzymes gluthation-peroxidase (GSH-Px) and superoxiddismutase (SOD) as well as concentration of thiobarbituric-acid reactive substances (TBARS). Incidence of liver metastases was 88.2% in Gr.2 (BOP/Aqua), it was decreased in Gr.4 (BOP/Octreo: 40%) and Gr.6 (BOP/SOM-230: 50%) (P < 0.05). Mean number/animal and mean-2-dimensional size of liver metastases did not differ between tumour groups. Comparing GSH-Px-activity in intrametastatic and extrametastatic hepatic tissue revealed a significant increase extrametastatically in Gr.2 (BOP/Aqua) and Gr.6 (BOP/SOM-230). SOD-activity in liver metastases was decreased in Gr.2 (1,801) (P < 0.05) versus Gr.4 (8,304) and Gr.6 (7,038). Intrametastatic TBARS concentration was increased in Gr.2 compared to Gr.4 (BOP/Octreotid) and Gr.6 (BOP/SOM-230) (P < 0.05). Octreotide and SOM-230 equally reduced liver metastasis in ductal pancreatic adenocarcinoma probably by a reduction of lipidperoxidation.
Kilian
M
M
Clinic of General, Visceral, Vascular and Thoracic Surgery, Universitätsmedizin in Berlin, Humboldt-University, Charité Campus Mitte, Schumannstr. 20/21, 10117, Berlin, Germany.
Gregor
J I
JI
Heukamp
I
I
Helmecke
K
K
Hanel
M
M
Wassersleben
B
B
Walz
M K
MK
Schimke
I
I
Kristiansen
G
G
Wenger
F A
FA
D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D006224:Cricetinae; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D015282:Octreotide / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017392:Thiobarbituric Acid Reactive Substances; D013004:Somatostatin; C517782:pasireotide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D015282:Octreotide