Preclinical studies on the anticancer activity of the somatostatin analogue octreotide (SMS 201-995).
The antiproliferative effect of somatostatin-14 and its analogue, octreotide, on in vitro pancreatic and breast tumor cells has led to the suggestion that octreotide may have further oncological indications in addition to its use in the treatment of gastroentero-pancreatic (GEP) tumors. To extend these in vitro observations, we evaluated the effect of octreotide in rodent models of pancreatic and breast tumors. Octreotide at a dose of 5 micrograms or 50 micrograms twice a day in nude mice bearing solid MiaPaCa pancreatic tumors (subline 21) or ZR-75-1 breast tumors induced a significant inhibition of tumor growth from week 2 until the end of treatment at week 5. After 5 weeks, the mean volume of ZR-75-1 tumors in animals treated with the 50-micrograms regimen was 48% of that in controls. Autoradiographic studies showed that a high percentage (71%) of ZR-75-1 tumors were somatostatin receptor-positive. In addition, the growth of ZR-75-1 cells in vitro was significantly inhibited by octreotide. The drug was also tested in a second breast cancer model, 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumors in rats, and continuous administration of 10 micrograms/kg/h over 6 weeks led to an approximate 50% reduction in the number of tumors arising in the rat mammary gland. These data suggest that pancreatic and breast cancer may be among the malignant diseases clinically susceptible to octreotide.
Weckbecker
G
G
Preclinical Research, Sandoz Pharma, Basel, Switzerland.
Tolcsvai
L
L
Liu
R
R
Bruns
C
C
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001345:Autoradiography; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015282:Octreotide / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D017481:Receptors, Somatostatin; D014407:Tumor Cells, Cultured
D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; D015127:9,10-Dimethyl-1,2-benzanthracene; D015282:Octreotide