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Preclinical studies on the anticancer activity of the somatostatin analogue octreotide (SMS 201-995)
G Weckbecker1, L Tolcsvai, R Liu
1Preclinical Research, Sandoz Pharma, Basel, Switzerland.
Abstract:
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.
Insights
Octreotide, a somatostatin analogue, significantly inhibited the growth of pancreatic and breast tumors in rodent models. These findings suggest octreotide may be a potential treatment for these cancers.
Area of Science:
- Oncology
- Pharmacology
Background:
- Octreotide exhibits antiproliferative effects on pancreatic and breast tumor cells in vitro.
- Current use of octreotide is primarily for gastroentero-pancreatic (GEP) tumors.
Purpose of the Study:
- To evaluate the in vivo efficacy of octreotide in preclinical models of pancreatic and breast cancer.
- To determine if octreotide has broader oncological applications beyond GEP tumors.
Main Methods:
- Administered octreotide to nude mice with MiaPaCa pancreatic and ZR-75-1 breast tumors.
- Assessed tumor growth inhibition and somatostatin receptor expression.
- Evaluated octreotide in a rat model of 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumors.
Main Results:
- Octreotide significantly inhibited pancreatic and breast tumor growth in mice.
- A 50-microgram regimen reduced ZR-75-1 tumor volume by 48% compared to controls.
- Octreotide reduced tumor incidence by approximately 50% in the DMBA-induced rat mammary tumor model.
Conclusions:
- Octreotide demonstrates significant anti-tumor activity in preclinical models of pancreatic and breast cancer.
- These findings support the potential clinical utility of octreotide for treating pancreatic and breast malignancies.