Octreotide (SMS 201-995) inhibits the growth of colon peritoneal carcinomatosis in BDIX rats.
In order to assess the effect of octreotide, a somatostatin analogue, on the growth of colon peritoneal carcinomatosis, 20 BDIX rats were injected i.p. with 1 x 10(6) colon cancer cells (DHD/K12 tumor cell line) and received octreotide, 65 micrograms/kg s.c. every 12 h (n = 10) or saline (n = 10) for 42 days, starting 3 days after tumor cell injection. Animals were killed at the end of the treatment. The mean volume of ascites was lower in the octreotide group (33.7 +/- 7.6 ml), than in the control group (67.5 +/- 16.3 ml; P < 0.05). The extent of peritoneal carcinomatosis (in five classes according to a previously published classification) was lower in the octreotide group (P < 0.05). Cell proliferation, using the BrdU technique, was markedly inhibited by octreotide (labeling index of tumor cells: 17.0 +/- 0.6% vs. 26.3 +/- 2.2% in controls, P < 0.001). No significant decrease in labeling index was observed in normal colonic mucosa. Two subtypes of somatostatin receptors were found in all tumors, using the 30F3 monoclonal antireceptor antibody. KD and Bmax values were not significantly different in the octreotide and control groups: high affinity, low capacity receptors (KD = 1.4 x 10(-10) M and 0.7 x 10(-10) M, respectively; Bmax = 3.8 and 2.9 pmol/mg protein, respectively); low affinity, high capacity receptors (KD = 1 +/- 0.2 x 10(-9) M and 5.5 +/- 0.05 x 10(-10) M, respectively; Bmax = 27.8 +/- 0.1 and 22.8 +/- 0.05 pmol/mg protein, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Ruszniewski
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P
Unité de Recherches de Gastroentérologie, Institut National de la Santé et de la Recherche Médicale U10, Hôpital Bichat, Paris, France.
Lehy
T
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Reyl-Desmars
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F
Le Roux
S
S
Lewin
M J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D015282:Octreotide / Q000494:pharmacology*; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017481:Receptors, Somatostatin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017481:Receptors, Somatostatin; D015282:Octreotide