Inhibitory Effects Of Octreotide On The Incursions And Metastasis Of Gastric Cancer In Vivo

Aims: To investigate the effects of somatostatin analogue octreotide on the growth of gastric cancer in vivo and the expressions of CD44v6, MMP-9, TIMP-1 and HIF-1αin gastric cancer tissues.Methods: A nude mouse model of xenografted human gastric cancer was established by implanting SGC-7901 human gastric cancer cells under the skin of nude mouse. Forty-eight experimental animals were randomly divided into four groups, 12 in each group: octreotide (octreotide 100μg/kg subcutaneously injected once daily), 5-Fu (5-Fu 17mg/kg intraperitonealy injected twice every week), combined group (octreotide plus 5-Fu of ditto dose), and control group (normal saline 20ul/mouse injected every day). At the end of the 6th week, the animals were executed and the xenotransplanted tissues were taken out to be examined pathologically, and the metastasis was observed simultaneously. The expressions of CD44v6, MMP-9, TIMP-1 and HIF-1αwere assessed by Elivision plus immunohistochemical technique respectively.Results: There was xenotransplanted in all nude mice, while only one mouse had a metastasis tumor in a distant subcutaneous position. No metastasis tumor was found in lymph node, liver, lung and the abdominal cavity in all mice. There was a significant difference in the positive percentage of CD44v6 and MMP-9 among the four groups (p=0.000, p=0.001 respectively). And the positive percentage of CD44v6 and MMP-9 in three trial groups were significantly higher than in control group (p<0.05). However, there was no significantdifference among octreotide , 5-Fu and combined group (p>0.05). There was a significant difference in the positive percentage of TIMP-1 among the four groups (p=0.047). Only in combined group was the positive percentage of TIMP-1 significantly higher than in control group (P<0.05). There were no significantly difference among three experiment groups (p>0.05). The expression percentage of HIF-1αin octreotide group, 5-Fu group, combined group and control group were of no significant difference (p=0.759>0.05).Conclusions: Octreotide could inhibit the growth and the expressions of CD44v6 and MMP-9 on gastric cancer, while up-regulated the expression of TIMP-1. There were synergistic action when octreotide was applied in treatment combined with 5-Fu. But Octreotide did not affect the expression of HIF-1α. These results suggest that octreotide and 5-Fu inhibit incursions and metastasis by inhibiting tumor cells attaching to extracellular matrix, decreasing tumor cell secreting MMP-9 and inhibiting its degradating extracellular matrix.