The in vitro synergistic cytotoxic effects of inductive, concurrent and sequential cyclooxygenase-2 inhibitor with cisplatin against A549 cell line

Abstract

9693 Background: Cyclooxygenase (COX)-2 inhibitors have been shown to exert antitumor activity against human lung cancer cell lines in vitro, and suppressive effect on lung tumors implanted into recipient mice, but concurrent use of COX-2 inhibitors and antineoplastic agents has not been proven clinically to be superior to chemotherapeutic agent alone. Sequential use of COX-2 inhibitors with chemotherapeutic agent might be a possible treatment option. We initiate in vitro study on the growth-inhibitory effect of inductive, concurrent and sequential celecoxib with cisplatin against A549 cell line to determine the most effective dose and schedule for maximal synergistic cytotoxic effects. We anticipate further appropriate treatment strategies to enhance the cytotoxic effect of chemotherapeutic agents using COX-2 inhibitors in the treatment of lung cancer. Methods: A549 cells were incubated with various concentration and combination of celecoxib and cisplatin for 4 days: celecoxib 24 hours prior to cisplatin as induction, celecoxib simultaneous with cisplatin as concurrent, and celecoxib 24 hours subsequent to cisplatin as sequential treatment. Time of exposure to cisplatin for all combination was 72 hours. Cell viability was determined using MTT assay. Results: The IC50 of cisplatin and celecoxib alone to A549 cell line was 16.64μM/l and 90.42μM/l, respectively. IC50 of cisplatin with celecoxib at 1.55μM/l for induction and concurrent treatment was 23.31μM/l, and 16.52μM/l, respectively, which was not superior to cisplatin alone while that of sequential treatment was 9.98μM/l, which showed synergistic cytotoxic effect against A549 cell line. Conclusions: Sequential celecoxib subsequent to cisplatin exerted the most potent in vitro synergistic cytotoxic effect against lung cancer cells. These may provide a rationale for future clinical trial to evaluate the effect of incorporating COX-2 inhibitors into the cisplatin-based regimen for the treatment of lung cancer. No significant financial relationships to disclose.