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Dependence of Indomethacin-induced Potentiation of Murine Tumor Radioresponse on Tumor Host Immunocompetence¹

Department of Experimental Radiotherapy [L. M., N. H., S. R.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

In a previous study (Furuta, Y., Hunter, N., Barkley, H. T., Jr., Hall, E., and Milas, L., Cancer Res., 48: 3008–3013, 1988), we demonstrated that inhibition of prostaglandins in murine tumors by indomethacin results in the augmentation of tumor response to single doses of ionizing radiation. The results of the present study show that indomethacin augmented tumor response to fractionated irradiation as well, the enhancement factor being more than 2. The effect of indomethacin on tumor growth and on tumor radioresponse was assayed in normal mice, mice deficient in T-cells (nude mice), and mice whose general immunocompetence was suppressed by whole-body irradiation. The antitumor activity of indomethacin was not significantly influenced by the immunocompetence of the tumor host. Since indomethacin inhibited tumor neoangiogenesis, we postulated that this inhibition is a major mechanism responsible for the antitumor activity of indomethacin. In contrast, potentiation of tumor radioresponse by indomethacin was greatly dependent on immunocompetence of tumor host: it was significantly reduced, or even abolished, when tumor grew in nude and whole-body irradiation mice. Thus, while immunocompetence of the tumor host has no significant effect on antitumor action by indomethacin, it plays a decisive role in the potentiation of tumor radioresponse by indomethacin.

¹ This investigation was supported by NIH Research Grant CA-06294. Animals used in this study were maintained in facilities approved by the American Association for Accreditation of Laboratory Animal Care and in accordance with current regulations and standards of the United States Department of Agriculture and Department of Health and Human Services.

² To whom requests for reprints should be addressed, at Department of Experimental Radiotherapy, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

³ Present address: Department of Surgery, University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, Japan 113.

⁴ Present address: School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan.

Received 1/ 8/90. Revised 4/12/90.

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