RT Journal Article SR Electronic T1 Inhibitory Effects of 5-Fluorouracil and Oxaliplatin on Human Colorectal Cancer Cell Survival Are Synergistically Enhanced by Sulindac Sulfide JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 435 OP 441 VO 29 IS 1 A1 SYLWIA FLIS A1 JACEK SPŁAWIŃSKI YR 2009 UL http://ar.iiarjournals.org/content/29/1/435.abstract AB Background: COX inhibitors appear to be promising agents in combination with cytostatics in the treatment of colorectal carcinoma (CRC). The aim of this study was to compare growth inhibitory effects of cytostatics (5-fluorouracil, 5-FU; oxaliplatin) and COX inhibitor sulindac sulfide (an active metabolite of sulindac), given alone or in combination, on several CRC cell lines. Materials and Methods: A series of human CRC cell lines were incubated with various combinations of the test drugs used in concentrations from 3 to 200 μM. The cell survival was assessed by MTT assay. Isobolograms and median effect method of Chou and Talalay were used to assess the nature and quantitative aspects of interaction observed between studied drugs. Cell cycle progression and apoptosis were measured using flow cytometric methods. In addition, growth inhibitory effects of studied agents on CRC cell lines were compared with a normal (mouse fibroblast) cell line. Results: Sulindac sulfide synergistically potentiated the inhibitory effects of 5-FU and oxaliplatin on CRC survival, parallel to the induction of apoptosis. A dose reduction effect for synergistic activity of sulindac sulfide with studied cytostatics (in the range of 5- to 14-fold, when compared to single agent) suggested that the inhibitory effect of cytostatics on CRC survival may be obtained at low doses. In addition, sulindac sulfide appeared to be more specific against CRC cells than normal cells. Conclusion: It was apparent that combination of 5-FU or oxaliplatin with sulindac sulfide results in a powerful inhibition of growth of colorectal carcinoma cells in vitro, which may be more specific for cancer than normal cells. Copyright© 2009 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved