title: The somatostatin analogue octreotide inhibits neuroblastoma growth in vivo.
abstract: Neuroblastoma, a neural crest-derived childhood tumor of the sympathetic nervous system, may in some cases differentiate to a benign ganglioneuroma or regress due to apoptosis. However, the majority of neuroblastomas are diagnosed as metastatic tumors with a poor prognosis despite intensive multimodal therapy. The neuropeptide somatostatin (SOM) has been shown to inhibit neuroblastoma growth and induce apoptosis in vitro. Therapeutic effects of SOM analogues are dependent on tumor expression of high-affinity receptors. In the present study, human neuroblastoma SH-SY5Y cells were grown as xenografts in nude rats. In vivo SOM receptor expression in the xenografts was identified using scintigraphy with 111In-pentetreotide. Rats were randomized to treatment with the long-acting SOM analogue octreotide (10 microg s.c. every 12 h), 13-cis-retinoic acid (4 mg orally every 24 h), or vasoactive intestinal peptide (40 microg s.c. every 24 h) and compared with controls. Tumor volume was assessed every second day and tumor weight after 10-12 d. Octreotide treatment inhibited neuroblastoma growth significantly with reduced tumor volumes at 10 and 12 d compared with untreated controls (mean 3.56 and 4.24 versus 6.48 and 8.01 mL, respectively; p < 0.01). Also, tumor weights after 10-12 d were reduced in octreotide-treated animals (n = 8, median weight 2.90 g, range 1.67-5.57 g) compared with untreated rats (n = 14, 7.54 g, 1.65-10.82 g, p = 0.005). Serum IGF-I decreased significantly over time both in rats treated with octreotide and in untreated controls. It is concluded that treatment with the SOM analogue octreotide may significantly decrease neuroblastoma tumor growth in vivo. Further studies are warranted to establish the role of SOM analogues in the treatment of children with unfavorable neuroblastoma.
authors.affiliation: Childhood Cancer Research Unit, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Borgström
authors.forename: M
authors.initials: M
authors.lastname: Hassan
authors.forename: E
authors.initials: E
authors.lastname: Wassberg
authors.forename: E
authors.initials: E
authors.lastname: Refai
authors.forename: C
authors.initials: C
authors.lastname: Jonsson
authors.forename: S A
authors.initials: SA
authors.lastname: Larsson
authors.forename: H
authors.initials: H
authors.lastname: Jacobsson
authors.forename: P
authors.initials: P
authors.lastname: Kogner
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology*; D015282:Octreotide / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011923:Rats, Nude
chemical_list: D018931:Antineoplastic Agents, Hormonal; D015282:Octreotide