Lanreotide promotes apoptosis and is not radioprotective in GH3 cells.
Somatostatin analogs are a mainstay of medical therapy in patients with GH producing human pituitary tumors, and it has been suggested that somatostatin analogs may be radioprotective. We utilized GH secreting rat GH3 cells to investigate whether a somatostatin analog may limit the effects of radiation on proliferation and apoptosis in vitro and on tumor growth in vivo. Treatment with lanreotide alone at doses of either 100 or 1000 nM for 48 h reduced clonogenic survival by 5-10%. Radiation alone produced a dose-dependent survival curve with a SF2 of 48-55%, and lanreotide had no effect on this curve. The addition of lanreotide resulted in a 23% increase in the proportion of apoptotic sub-G1 cells following irradiation (P<0.01). In a mouse GH3 tumor xenograft model, lanreotide 10 mg/kg moderately inhibited the growth of GH3 tumors, with a 4x tumor growth delay (TGD) time that ranged from 4.5 to 8.3 days. Fractionated local tumor radiation alone significantly inhibited tumor growth and produced a TGD of 35.1+/-5.7 days for 250 cGy fractions. The combination of lanreotide, either antecedent to or concurrent, with radiation of 250, 200 or 150 cGy/fraction for 5 days inhibited tumor growth and produced the TGD times that were similar to radiation alone (P>0.05). Pretreatment with lanreotide had the most significant radiosensitizing effect. These studies demonstrate that the somatostatin analog lanreotide is not radioprotective in GH3 cells, and further studies are necessary to determine the impact of lanreotide on apoptosis.
Ning
Shoucheng
S
Department of Radiation Oncology, Stanford University School of Medicine, Stanford University Medical Center, 875 Blake Wilbur Drive, Stanford, California 94305-5821, USA.
Knox
Susan J
SJ
Harsh
Griffith R
GR
Culler
Michael D
MD
Katznelson
Laurence
L
D000236:Adenoma / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D005720:Gamma Rays; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000187:drug effects*; D011837:Radiation-Protective Agents / Q000494:pharmacology; D051381:Rats; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D052683:Somatotrophs / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; D011837:Radiation-Protective Agents; C060347:lanreotide; D013004:Somatostatin