Objective: To investigate whether EGFR inhibitor AG1478 combined with celecoxib could enhance the inhibitive effects on the growth of gastric cancer cells.
Methods: Human gastric cancer cell line SGC-7901 was cultured and treated with different concentration of AG1478 and celecoxib, the proliferation of SGC-7901 cells was determined by MTT. The expression of proliferation cell nuclear antigen (PCNA) of SGC-7901 cells was detected by immunocytochemistry. ERK and p-ERK expression were determined by immunoblot. The TdT-mediated dUTP nick end labeling (TUNEL) assay was used to detect apoptosis.
Results: When SGC-7901 cells was treated with AG1478 or celecoxib alone, cell growth was only inhibited by high concentration of the two agents (10, 100 micromol/L) significantly, the IC50 of AG1478 and celecoxib were 69.69 micromol/L and 70.98 micromol/L respectively. Compared with AG1478 or celecoxib alone, combination of AG1478 and celecoxib at different doses significantly enhanced the inhibitive effects on cell growth (P < 0.01). Compared with control (56. 55%), the expression of PCNA was decreased in the cells treated with AG1478, celecoxib and the combination of these two agents, PCNA indeices were 26.24%, 38.16%, and 9.08%, respectively (P < 0.01). AG1478 induced cell apoptosis at 10 micromol/L, the rate was 7.88% vs. 3.54% in control (P < 0.01), and the combination of AG1478 with celecoxib showed an enhanced effect, the apoptosis rate was 14.90%. There were no any effects on ERK expression with the treatments of either AG1478, celecoxib alone or toghether, but the phospholation of ERK was decreased by AG1478 (P < 0.01).
Conclusion: AG1478 combined with celecoxib results in enhanced inhibitive effect on the growth of SGC-7901, which may partly due to the suppression of ERK phospholation.