Objective: To investigate the anti-tumor effect of celecoxib combined with tegafur gimeracil oteracil potassium on subcutaneous xenograft tumor of gastric cancer in nude mice and analyze the possible mechanism.
Methods: A xenograft tumor model of gastric cancer was established subcutaneously in nude mice. After the largest diameter of tumor reached about 5 mm, the nude mice were randomly divided into 4 groups: the control group, the celecoxib group, the tegafur gimeracil oteracil potassium group, and the combination group; the drug was administered respectively for 21 days. Thereafter, tumor tissues were collected, tumor volume was measured, and tumor inhibition rate was calculated. Apoptosis was determined by TUNEL assay and the expression levels of PCNA, Bcl-2 and caspase-3 by immunohistochemistry.
Results: The tumor inhibition rates of the celecoxib group, the tegafur gimeracil oteracil potassium group, the combination group were 30.8%, 50.1%, 78.8%, respectively. The apoptosis index in treatment groups was higher than that in the control group (P<0.01), and the combination group was higher than single drug group (P<0.01). The expressions of PCNA, Bcl-2 in treatment groups were lower than those in the control group (P<0.01), and the combination group was lower than single drug group (P<0.05). The expression of caspase-3 in treatment groups was higher than that in the control group (P<0.05), and the combination group was higher than single drug group (P<0.01).
Conclusion: Both celecoxib and tegafur gimeracil oteracil potassium showed obvious anti-tumor effect, and the combination of the two acted synergistically. The possible mechanism was that they inhibited tumor growth through inhibiting proliferation and promoting apoptosis of the tumor cells.