Enhancement of tamoxifen-induced suppression of insulin-like growth factor I gene expression and serum level by a somatostatin analogue

Biochem Biophys Res Commun. 1994 Aug 30;203(1):253-9. doi: 10.1006/bbrc.1994.2175.

Abstract

Mitogenic responsivity of many neoplasms to IGF-I has been detected in a variety of in vivo and in vitro experimental systems. This has led to the proposal that pharmacological reduction of IGF-I bioactivity might represent a novel non-cytotoxic palliative therapy. We recently reported that tamoxifen, a commonly used antiestrogen antineoplastic agent, significantly suppresses IGF-I gene expression and serum IGF-I levels. We report here that the somatostatin analogue octreotide, previously demonstrated to reduce acromegalic levels of IGF-I towards normal, decreased serum IGF-I to 70 +/- 4% (mean +/- SD) of control values and hepatic IGF-I expression to 65 +/- 10% of control values in a short-term non-acromegalic rat model. Tamoxifen reduced serum IGF-I to 74 +/- 12% of control values and hepatic IGF-I expression to 46 +/- 9% of control values in this model, but the combination of octreotide and tamoxifen reduced serum IGF-I concentration to 49 +/- 10% of control values and hepatic IGF-I gene expression to 12 +/- 9% of control values. The levels of serum IGF-I and hepatic IGF-I gene expression were significantly less in animals treated with the combination of octreotide and tamoxifen than in animals treated with either agent alone (p < .01). This combination represents a novel pharmacological strategy for suppressing IGF-I gene expression that may be relevant to the design of clinical trials.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Drug Interactions
  • Female
  • Gene Expression* / drug effects
  • Insulin-Like Growth Factor I / biosynthesis*
  • Insulin-Like Growth Factor I / metabolism
  • Liver / drug effects
  • Liver / metabolism*
  • Octreotide / pharmacology*
  • RNA, Messenger / biosynthesis
  • Radioimmunoassay
  • Rats
  • Rats, Sprague-Dawley
  • Tamoxifen / pharmacology*

Substances

  • RNA, Messenger
  • Tamoxifen
  • Insulin-Like Growth Factor I
  • Octreotide