[Inhibitory effects of celecoxib combined with octreotide on growth of multidrug resistant human gastric cancer cell line SGC7901/ADR].

BACKGROUND & OBJECTIVE: Both cyclooxygenase-2 (COX-2) inhibitor and octreotide can inhibit growth of tumor cells. This study was to investigate inhibitory effects of COX-2 inhibitor celecoxib alone, and celecoxib combined with octreotide on growth of multidrug resistant human gastric cancer cell line SGC7901/ADR.

METHODS

Experimental groups:(1)celecoxib (1 x 10(-4)-1 x 10(-8) mol/L); (2)octreotide (1 x 10(-5)-1 x 10(-9) mol/L); (3)celecoxib (1 x 10(-4)-1 x 10(-8) mol/L) combined with octreotide (1 x 10-6 mol/L);(4)control group (RPMI-1640 medium without serum). The effects of all treatments on SGC7901 cells, and SGC7901/ADR cells were observed. Cell proliferation was measured by (3)H-thymidine incorporation into DNA. The expression of proliferating cell nuclear antigen (PCNA) was detected by immunocytochemistry. Cell apoptosis was measured by TdT-mediated dUTP nick end-labeling assay (TUNEL) and flow cytometry.

RESULTS

(3)H-thymidine incorporation into SGC7901/ADR cells treated with celecoxib [(471.3+/-79.7) cpm] was significantly lower than that of control group [(917.5+/-130.8) cpm](P< 0.05). When combined with octreotide, celecoxib presented lower (3)H-thymidine incorporation [(220.0+/-19.7)cpm] than it alone with a 53.3% decrease. The concentration of celecoxib in combination group negatively related to synthesis of DNA in SGC7901/ADR cells (r=0.996,P< 0.001). The expression of PCNA in either celecoxib group or combination group markedly decreased. The apoptosis rates of SGC7901/ADR cells induced by celecoxib alone, and combination treatment were 32.9%, and 52.5%.

CONCLUSION

Celecoxib combined with octreotide may enhance inhibition of growth of multidrug resistant human gastric cancer cells. The mechanism may be related with inhibiting DNA synthesis, and inducing apoptosis.