Short-term octreotide treatment induces apoptosis in human pancreatic cancer xenografts.
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 (2x100 microg/kg b.w.) administered in a short-term (4-day) experiment were investigated.


METHODS
CBA immunosuppressed mice bearing human pancreatic carcinoma (PXZ-40/6) were treated daily with 2x100 microg/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.


CONCLUSIONS
The results suggest that low doses of octreotide induce apoptosis in human pancreatic cancer xenografts after a short-term treatment.
Zalatnai
Attila
A
Semmelweis University, Faculty of Medicine, First Department of Pathology and Experimental Cancer Research, Budapest, Hungary. zalatnai@korb1.sote.hu
Bocsi
József
J
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007279:Injections, Subcutaneous; D051379:Mice; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D015282:Octreotide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
D018931:Antineoplastic Agents, Hormonal; D015282:Octreotide