Synergistic Effect of Indomethacin with Adriamycin and Cisplatin on Tumor Growth

Abstract

In this study, we have examined the antitumor effect of combined administrations of indomethacin (IND) with chemotherapeutic drugs on tumor growth. Colon 26 clone 20 (C20) cells and monocyte chemotactant protein-1 (MCP-1) transfected C20 cells (C20βA-2-1) were used and these cells were inoculated into the footpad of BALB/c mice. At day 1 after tumor inoculation, treatment with 0.001% IND via the drinking water was commenced. At days 4, 6, and 8, adriamycin or cisplatin was administered intravenously at a dose of 5 mg/kg or intraperitoneally at a dose of 2 mg/kg, respectively. Although IND, adriamycin and cisplatin only partially reduced the growth of the C20 tumors after treatment with each drug on its own, a marked synergistic effect was observed when they were given in combination. A synergistic effect between IND and cisplatin on C20βA-2-1 was also observed. However, IND itself showed no suppression of C20βA-2-1 tumor growth. These results suggest that combination of indomethacin with chemotherapeutic drugs could be an effective form of cancer chemotherapy. The observed effects may be dependent on the expression of MCP-1.