EFFECTS OF THE ACTH(4-9) ANALOG, ORG-2766, ON VINCRISTINE CYTOTOXICITY IN 2 HUMAN LYMPHOMA CELL-LINES, U937 AND U715

The use of cytotoxic drug vincristine (VCR) is limited by the occurren ce of peripheral neuropathy. A neurotrophic ACTH(4-9) analogue, ORG 27 66, is being studied for its protective effect. Possible modulatory ef fects of ORG 2766 on tumour cell growth and interference with the cyto toxic efficacy of VCR were studied in two human lymphoma cell lines, U 937 and U715. The effects of ORG 2766 on cell growth and survival and on VCR-mediated cytotoxicity were investigated using two MTT-based ass ays to study direct cytotoxic effects and to assess residual growth af ter pretreatment. Treatment with ORG 2766 alone had no effect on cell growth and survival. Neither did this drug affect VCR cytotoxicity. Ho wever, after 96 h pretreatment with ORG 2766 and a culture period of 7 days, a reduction in residual growth and a potentiation of VCR-induce d inhibition of growth capacity was observed in U715 cells, and to som e extent also in U937 cells. It is concluded that ORG 2766 has no stim ulatory effects on tumour growth and does not negatively interfere wit h VCR-mediated cytotoxicity. Rather it enhances the cytostatic effect of VCR. It is suggested that ORG 2766 can safely be used in clinical t rials investigating the ability of ORG 2766 to counteract VCR-induced neurotoxicity.