Apoptosis-induction and phosphorylation state in human pancreatic carcinoma xenografts following octreotide treatment.
BACKGROUND
Some exocrine pancreatic carcinomas are responsive to hormonal manipulations, but the mechanism is not fully understood.


METHODS
Human pancreatic cancer xenografts (PZX-15/F4) grown in immunosuppressed mice were treated with Sandostatin (2 x 100 micrograms/b.w. s.c.) for 4 weeks. Mitotic and apoptotic activities were assessed and supplemented with immunohistochemical detection of phosphotyrosine and bcl-2 protein.


RESULTS
In the treated group 5/16 tumors exhibited a 20-68% volume reduction, and the number of apoptotic cells was significantly increased (18.1 +/- 3.1/mm2 vs. 6.2 +/- 1.1/mm2 in controls, P < 0.0012). At the same time, a highly significant reduction in the number of the phosphotyrosine-positive tumor cells was observed (40.9% from 64.9%; P < 0.0001). The mitotic activity did not change significantly. Both the untreated and the treated tumors proved to be bcl-2 negative.


CONCLUSIONS
The results indicated that the octreotide triggered an apoptosis-induction in a human pancreatic cancer xenograft, coupled with the increased dephosphorylation state in the tumors, but the mitotic activity was not affected and bcl-2 expression has not been induced.
Zalatnai
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A
1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, H-1085 Budapest, Ullöi út 26, Hungary. zalatnai@korbl.sote.hu
Pogány
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V
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D008940:Mitotic Index; D015282:Octreotide / Q000494:pharmacology* / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D018931:Antineoplastic Agents, Hormonal; D019000:Phosphotyrosine; D015282:Octreotide