Effects of somatostatin analogs octreotide and lanreotide on the proliferation and apoptosis in colon 38 tumor: interaction with 5-fluorouracil.

: OBJECTIVES: The aim of this study was to compare the effects of two somatostatin (SS) analogs: octreotide and lanreotide administered separately or together with 5-fluorouracil (5-FU) with the action of 5-FU alone, on proliferation, apoptosis, proliferation/apoptosis (P/A) ratio and tumor weight in the murine transplantable Colon 38 cancer. MATERIALS AND METHODS: Two separate experiments were performed on male mice of B6D2F1 strain. In both experiments the animals were implanted subcutaneously with suspension of Colon 38 cancer cells. A few days later, in the first experiment, octreotide was given once daily for six days at the dose of 10 &mgr;g/animal and in the second experiment a single dose of lanreotide (1 mg/animal) was administered. 5-FU was treated once (in the first experiment) or twice (in the second experiment) at the dose of 70 mg/kg b.w. depending on the duration of the experiment. In both experiments the incorporation of bromodeoxyuridine into the tumor cell nuclei was used as an index of cell proliferation (labeling index - LI). The labeling of nuclear DNA fragmentation according to TUNEL method was considered as an index of apoptosis (AI). RESULTS: It has been found that both SS analogs, given separately, significantly decreased LI of tumor cells, increased their AI and decreased P/A ratio of Colon 38 tumors, as compared to controls. 5-FU given alone (in both experiments) significantly enhanced AI, decreased P/A ratio, but did not significantly change LI, as compared to controls. The joint treatment with 5-FU and each of the two SS analogs did not produce any additive effects either on proliferation or apoptosis. The tumor weight was significantly decreased only by the joint treatment with 5-FU and octreotide, as compared to the control group.