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Preclinical studies on the anticancer activity of the somatostatin analog octreotide (SMS 201-995)
G Weckbecker1, L Tolcsvai, R Liu
1Preclinical Research, Sandoz Pharma Ltd., Basle, Switzerland.
Abstract:
The antiproliferative effect of somatostatin-14 and its analog octreotide on in vitro pancreatic and breast tumor cells has led to the suggestion that octreotide may have further oncological indications in addition to gastroenteropancreatic tumors. To extend these in vitro observations, we evaluated the effect of octreotide in rodent models of pancreatic and breast tumors. Octreotide of 5 or 50 micrograms b.i.d. in nude mice bearing solid MiaPaCa pancreatic tumors (subline 21) or ZR-75-1 breast tumors induced 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% that of control. Autoradiographic studies showed a high percentage (71%) of ZR-75-1 tumors to be 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, DMBA-induced mammary tumors in rats, and continuous administration of 10 micrograms/kg/h over 6 weeks led to an approximately 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 analog, demonstrated significant antiproliferative effects in rodent models of pancreatic and breast tumors. These findings suggest octreotide
Area of Science:
- Oncology
- Pharmacology
- Endocrinology
Background:
- Somatostatin-14 and octreotide exhibit antiproliferative effects on pancreatic and breast tumor cells in vitro.
- This suggests potential oncological applications for octreotide beyond gastroenteropancreatic tumors.
Purpose of the Study:
- To evaluate the in vivo efficacy of octreotide in rodent models of pancreatic and breast cancer.
- To extend in vitro observations to preclinical in vivo settings.
Main Methods:
- Rodent models were used, including nude mice with MiaPaCa pancreatic tumors and ZR-75-1 breast tumors.
- Octreotide was administered at various doses (5 or 50 micrograms b.i.d.) and durations (5-6 weeks).
- Tumor growth inhibition, volume reduction, and tumor incidence were assessed. Autoradiography identified somatostatin receptor expression.
Main Results:
- Octreotide significantly inhibited tumor growth in both pancreatic (MiaPaCa) and breast (ZR-75-1) cancer models.
- ZR-75-1 tumors treated with 50 micrograms octreotide showed a 48% reduction in mean volume compared to controls.
- Autoradiography confirmed high somatostatin receptor positivity (71%) in ZR-75-1 tumors. Octreotide also reduced DMBA-induced mammary tumors in rats by approximately 50%.
Conclusions:
- Octreotide demonstrates significant in vivo antitumor activity against pancreatic and breast cancer models.
- These findings support the potential clinical utility of octreotide for treating pancreatic and breast malignancies.
- Somatostatin receptor status may predict response to octreotide therapy in these cancers.