Octreotide (SMS 201–995) inhibits the growth of colon peritoneal carcinomatosis in BDIX rats

Abstract

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 1·10 6 colon cancer cells (DHD/K12 tumor cell line) and received octreotide, 65 μg/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. K D and B max values were not significantly different in the octreotide and control groups: high affinity, low capacity receptors ( K D =1.4·10 −10 M and 0.7·10 −10 M , respectively; B max =3.8 and 2.9 pmol/mg protein, respectively); low affinity, high capacity receptors ( K D =1±0.2·10 −9 M , respectively; B max =27.8±0.1 and 22.8±0.05 pmol/mg protein, respectively). Octreotide inhibits the growth of colon peritoneal carcinomatosis in vivo in BDIX rats through an inhibition of DNA synthesis; this effect is at least partly mediated by somatostatin receptors present on tumor cells.