POTENTIATION OF ANTITUMOR AND ANTIMETASTATIC ACTIVITIES OF ALPHA-DIFLUOROMETHYLORNITHINE BY INTERFERON INDUCERS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (7) , 2799-2802
Abstract
The potentiation of antitumor and antimetastatic activities of DL-.alpha.-difluoromethylornithine (DFMO) by tilorone and polyriboinosinic:polyribocytidilic acid complex [poly(1) .cntdot. poly(C)] was studied. These interferon inducers enhance the antitumor activity of DFMO against B16 [murine] melanoma cells when administered alone; however, a combination of DFMO and tilorone or poly(1) .cntdot. poly(C) resulted in greater inhibition of growth, with .apprx. 20% of the animals showing no detectable tumors. This potentiation appears to be related to the ability of the compounds to induce interferon. This combination is particularly efective when the tumor burden is relatively low. Studies with Lewis lung carcinoma showed that DFMO or tilorone administered alone inhibited tumor growth and metastases. Poly(1) .cntdot. poly(C) alone had no effect on tumor growth and metastases. A combination of DFMO and tilorone potentiated inhibition of tumor growth and metastases. A combination of DFMO and poly(1) .cntdot. poly(C) showed a lesser potentiation of both antitumor activity and antimetastatic activity. The mechanism underlying this tumor suppression by combination of DFMO and interferon inducers is not yet known. There seems to be a potential use for the inhibitors of polyamine biosynthesis in combination with interferon or interferon inducers in cancer chemotherapy.

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