NSAID Indomethacin Enhanced Cytostatic Effect of Cis-Platinum of the Proliferation of Prostaglandin Producing and Non-Producing Cancers in Cell Line

Non-steroidal anti-inflammatory drug, INDOMETHACIN, a potent cyclooxygenase inhibitor, has been recently regarded as biological response modifier in that it inhibits the production of immunosuppressing prostaglandins, among which prostaglandin E2 has been shown to play a clear role in the regulation of lymphokine production and considered as being involved in the suppression of immune response system (1). Therefore, indomethacin has been thought to exert its anti-tumor effect through stimulating cellular immune function by inhibiting the formation of immunosuppressing prostaglandins (2). In the early 80’s, some papers have reported the anti-tumor effect of indomethacin by in vivo studies (3) (4). Furthermore, in the other works, indomethacin has been revealed to enhance the immunocompetence (5) (6). In this way, most of these documents attributed to the anti-tumor effect of indomethacin to the inhibition of increased formation of immunosuppressing prostaglandin E2 by the cancer per se and/or as a result of paraneoplastic manifestation. However, there have been a very few number of papers issued reporting direct cytostatic effect of indomethacin. In the present study, we obtained prostaglandin producing and non-producing cell lines of the uterine cervical cancer, then we assessed the changes in cell growth of the cancer when indomethacin was added to the culture medium. Moreover, we investigated whether or not additional cytostatic effect would be expected if indomethacin was used in combination with cis-platinum.