Dependence of indomethacin-induced potentiation of murine tumor radioresponse on tumor host immunocompetence.
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.
Milas
L
L
Department of Experimental Radiotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Furuta
Y
Y
Hunter
N
N
Nishiguchi
I
I
Runkel
S
S
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005354:Fibrosarcoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D007213:Indomethacin / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D011838:Radiation-Sensitizing Agents; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*
D011838:Radiation-Sensitizing Agents; D007213:Indomethacin