Apoptosis-induction and phosphorylation state in human pancreatic carcinoma xenografts following octreotide treatment

Anticancer Res. 2001 Jan-Feb;21(1A):477-80.

Abstract

Background: Some exocrine pancreatic carcinomas are responsive to hormonal manipulations, but the mechanism is not fully understood.

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Apoptosis / drug effects*
  • Carcinoma / drug therapy
  • Carcinoma / metabolism
  • Carcinoma / pathology*
  • Humans
  • Mice
  • Mitotic Index
  • Octreotide / pharmacology*
  • Octreotide / therapeutic use
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Phosphorylation / drug effects
  • Phosphotyrosine / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Hormonal
  • Phosphotyrosine
  • Octreotide