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Prostaglandin Production by Murine Tumors as a Predictor for Therapeutic Response to Indomethacin¹

Departments of Experimental Radiotherapy [Y. F., L. M.] and Clinical Radiotherapy [T. B.], The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, Texas; and Department of Internal Medicine, University of Texas Medical School, Houston, Texas [E. R. H., S. S.]

We investigated whether there is a relationship between the production of eicosanoids by murine solid tumors and their response to the prostaglandin H (PGH) synthase inhibitor indomethacin. Three sarcomas, designated FSA, NFSA, and SA-NH, and two carcinomas, designated MCA-K and HCA-I, syngeneic to C3Hf/Kam mice were used. In general, FSA and NFSA produced more PGH synthase products than lipoxygenase products, whereas HCA-I produced both types of metabolites in large quantities. All three tumors responded well to indomethacin treatment by slowing their growth. In contrast, MCA-K and SA-NH tumors produced insignificant quantities of PGH synthase products, but substantial amounts of lipoxygenase products. Their growth was not affected by treatment with indomethacin. Indomethacin did not influence tumor cell survival either in vitro or in vivo, but it reduced the proportion of S-phase cells in the tumors. The antitumor effect of indomethacin was not reduced by immunosuppression of the tumor host and was independent of tumor immunogenicity, implying that indomethacin acted through nonimmunological mechanisms. Thus, the effectiveness of indomethacin was directly related to the ability of tumors to produce PGs. Consequently, the eicosanoid profile of tumors could serve as a valuable way to select patients likely to respond to indomethacin and other PGH synthase inhibiting agents.

¹ This investigation was supported in part by NIH Research Grant CA-06294, awarded by the National Cancer Institute, and P01-NS-18494, awarded by National Institute for Neurological and Communicative Disorders and Stroke. Elizabeth R. Hall is a recipient of a Research Career Development Award (K04-NS00873). 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 U. S. 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 Hospital and Tumor Institute at Houston, P. O. Box 66, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 11/ 2/87. Revised 2/19/88. Accepted 2/22/88.

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