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Somatostatin receptor-dependent growth inhibition of liver metastases by octreotide
C H van Eijck1, G D Slooter, L J Hofland
1Department of Surgery, University Hospital Dijkzigt, Rotterdam, The Netherlands.
Abstract:
Rats were administered the somatostatin analogue octreotide 15 micrograms intraperitoneally twice daily for 4 weeks after intraportal injection of somatostatin receptor-positive pancreatic tumour cells (CA-20948) and somatostatin receptor-negative colonic tumour cells (CC531). Octreotide significantly inhibited the growth and development of somatostatin receptor-positive tumour cells in the liver. The median number of liver tumours was 286 (range 146 to greater than 500) in the treated animals and more than 500 (range 250 to in excess of 500) in the controls (P < 0.05). This significant difference in tumour load was also represented in the mean(s.e.m.) liver weight (14.5(3.7) g in animals given octreotide versus 17.9(3.0) g in the controls). No effect of octreotide treatment was found on the growth and development of somatostatin receptor-negative tumour cells in the liver. The median (range) number of tumours was 6.5 (0-425) in the treated animals and 11.0 (0-475) in the controls. Mean(s.e.m.) liver weights were 14.0(5.7) g and 11.8(4.5) g respectively. There was no difference in serum levels of growth hormone, prolactin and insulin-like growth factor between control and octreotide-treated rats. The growth inhibition of somatostatin receptor-positive tumour cells was unlikely to be the result of suppressed secretion of one of these tumour growth factors. Octreotide may be useful for the treatment of patients with somatostatin receptor-positive hepatic metastases, which can be demonstrated by somatostatin receptor scintigraphy.
Insights
Octreotide, a somatostatin analogue, effectively inhibited the growth of somatostatin receptor-positive liver tumors in rats. This treatment showed no effect on receptor-negative tumors, suggesting targeted therapeutic potential.
Area of Science:
- Oncology
- Pharmacology
- Gastroenterology
Background:
- Somatostatin receptor-positive tumors, such as pancreatic and colonic tumors, can metastasize to the liver.
- Octreotide is a somatostatin analogue with potential antitumor effects.
- The efficacy of octreotide in treating hepatic metastases is under investigation.
Purpose of the Study:
- To evaluate the effect of octreotide on the growth of somatostatin receptor-positive and -negative liver tumors in a rat model.
- To determine if octreotide's efficacy is specific to tumors expressing somatostatin receptors.
Main Methods:
- Rats received intraportal injections of somatostatin receptor-positive (CA-20948) and somatostatin receptor-negative (CC531) tumor cells.
- Animals were treated with octreotide (15 micrograms intraperitoneally twice daily) or a placebo for 4 weeks.
- Tumor load was assessed by counting liver tumors and measuring liver weight. Serum levels of growth hormone, prolactin, and insulin-like growth factor were also measured.
Main Results:
- Octreotide significantly reduced the number and load of somatostatin receptor-positive liver tumors compared to controls (median 286 vs. >500 tumors).
- Octreotide treatment did not affect the growth of somatostatin receptor-negative liver tumors (median 6.5 vs. 11.0 tumors).
- No significant differences in serum growth hormone, prolactin, or insulin-like growth factor levels were observed between treated and control groups.
Conclusions:
- Octreotide demonstrates significant inhibitory effects on the growth of somatostatin receptor-positive hepatic tumors.
- The antitumor effect of octreotide appears to be specific to tumors expressing somatostatin receptors.
- Octreotide may be a valuable therapeutic option for patients with somatostatin receptor-positive hepatic metastases, detectable via scintigraphy.