Flow cytometric evidence of apoptosis in human pancreatic cancer xenografts treated with sandostatin (octreotide)

Background: The antiproliferative effect of octreotide (Sandostatin) is par tly attributed to induction of apoptosis in the given tumors. In this work, apoptosis was assessed in human pancreatic carcinoma xenografts after a 4- week high-dose Sandostatin treatment. Materials and Methods: Subcutaneously growing human pancreatic cancel xenografts (PZX-5) in immunosuppressed mic e were treated with 500 mu g/kgb.w. Sandostatin twice a day ip. for 4 weeks . Apoptosis was evaluated by means of conventional histology, Apoptag-immun ohistochemistry and flow cytometry. Results: The Sandostatin-treatment resu lted in a decreased tumor volume in 9 out of 16 animals. Immunohistochemica l defection of apoptosis by Apoptag revealed a 75-fold increase of the posi tively stained tumorous nuclei (210.9 +/- 53.9 per square mm) versus non-tr eated tumors (2.5 +/- 0.5 per square mm). The sub-GI fi action was 3.61 +/- 0.4 % in untreated samples while it doubled after treatment (p < 0.001) Co nclusion: A 4-week octreotide (Sandostatin) treatment induced significantly increased apoptosis in human pancreatic carcinoma xenografts evidenced by morphological studies and Apoptag-immunohistochemistry, and these results w ere clearly reinforced by flow cytometry.