Objective: To investigated if cyclooxygenase-2 (COX-2) inhibitor celecoxib in combination with somatostatin (SST) analog octreotide is able to inhibit the metastasis of human gastric cancer (GC) in vivo.
Methods: Seventy five patients with GC were randomly divided into 3 equal groups: control group, taking no anti-tumor medicine before GC resection; celecoxib group, receiving celecoxib orally 200 mg/d for 7 days before surgery; and combination group, receiving celecoxib orally 200 mg/d and octreotide 100 microg injected subcutaneously for 7 days before operation. The resected specimens were studied for the expression of epithelial cadherin (E-Cad) and matrix metalloproteinase (MMP) by using immunohistochemical staining. MMP-2 and MMP-9 were also quantified with Western blotting. The GC cells from the resected gastric cancer specimens were isolated by immunomagnetic separation. Modified Boyden chamber membrane invasion culture system coated with Matrigel was used to observe the migration and invasion of the GC cells.
Results: The abnormal staining rates of E-Cad of GC tissue in the combination group and the celecoxib group were 28.0% and 44.0%, significantly lower than that in the control group (56.0%, both P < 0.05). The grey level of MMP-2 and MMP-9 in the combination and celecoxib groups were (99 +/- 20, 89 +/- 13) and (260 +/- 15, 180 +/- 13) respectively, both significantly lower than that of the control group [(314 +/- 11, 241 +/- 12), P < 0.05]. The number of GC cells that penetrated the membrane was (2.75 +/- 0.58)/10(3) cells in the combination group, (2.29 +/- 0.58)/10(3) cells, the migration rate of the combination group was lower by 38% compared with that of the control group (F = 6.44, P < 0.05).
Conclusion: The metastasis of human gastric carcinoma cells may be inhibited by the combinative treatment of celecoxib and octreotide.