Enhancement of tamoxifen-induced suppression of insulin-like growth factor I gene expression and serum level by a somatostatin analogue.
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.
Huynh
H
H
Department of Medicine, Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, Canada.
Pollak
M
M
D000818:Animals; D015152:Blotting, Northern; D004347:Drug Interactions; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D015282:Octreotide / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology*
D012333:RNA, Messenger; D013629:Tamoxifen; D007334:Insulin-Like Growth Factor I; D015282:Octreotide