Short-term Octreotide Treatment Induces Apoptosis in Human Pancreatic Cancer Xenografts

Abstract

Background: It was previously demonstrated that octreotide (Sandostatin) induced an increased apoptotic activity in human pancreatic cancer xenografts after a high dose, 1-month treatment. In the present study the effect of smaller doses (2×100 μg/kg b.w.) administered in a short-term (4-day) experiment were investigated. Materials and Methods: CBA immunosuppressed mice bearing human pancreatic carcinoma (PXZ-40/6) were treated daily with 2×100 μg/kg b.w. Sandostatin subcutaneously for 4 consecutive days. The number of tumor cells displaying apoptotic bodies (late event) and mitotic activity were assessed by morphometry, while the earlier phase of the apoptotic process was determined using flow cytometry. Results: A short octreotide treatment did not influence the mitotic activity, but the number of apoptotic cells decreased significantly (1.8±0.44/mm² in controls vs. 6.8±1.0/mm² in treated tumors, p<0.0009). The percentage of nuclei in sub-G1 phase almost doubled (6.0±0.75% in controls, 11.2±0.97% in the octreotide-treated group, p<0.0014). The DNA index and the proliferation indices proved to be unchanged. Conclusion: The results suggest that low doses of octreotide induce apoptosis in human pancreatic cancer xenografts after a short-term treatment.