Flow cytometric evidence of apoptosis in human pancreatic cancer xenografts treated with Sandostatin (octreotide).
BACKGROUND
The antiproliferative effect of octreotide (Sandostatin) is partly 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.


METHODS
Subcutaneously growing human pancreatic cancer xenografts (PZX-5) in immunosuppressed mice were treated with 500 micrograms/kgb.w. Sandostatin twice a day i.p. for 4 weeks. Apoptosis was evaluated by means of conventional histology, Apoptag-immunohistochemistry and flow cytometry.


RESULTS
The Sandostatin-treatment resulted in a decreased tumor volume in 9 out of 16 animals. Immunohistochemical detection of apoptosis by Apoptag revealed a 75-fold increase of the positively stained tumorous nuclei (210.9 +/- 53.9 per square mm) versus nontreated tumors (2.8 +/- 0.5 per square mm). The sub-G1 fraction was 3.61 +/- 0.4% in untreated samples while it doubled after treatment (p < 0.001).


CONCLUSIONS
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 were clearly reinforced by flow cytometry.
First Institute of Pathology and Experimental Cancer Research, Semmelweis University of Medicine, Budapest VIII, Hungary. zalatnai@korb1.sote.hu
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Zalatnai
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Szegedi
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D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D017209:Apoptosis; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D016867:Immunocompromised Host; D007124:Immunoenzyme Techniques; D051379:Mice; D009368:Neoplasm Transplantation; D015282:Octreotide / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014183:Transplantation, Heterologous
D018931:Antineoplastic Agents, Hormonal; D015282:Octreotide