ENHANCEMENT OF ANTIPROLIFERATION ACTIVITY OF VINCRISTINE AND ADRIAMYCIN BY INTERFERON

Abstract

Vincristine (VCR) combined with interferon (IFN)-β suppressed H. Ep #2 cell proliferation more than additively, whereas 6-mercaptopurine combined with IFN-β suppressed it less than additively. Factors associated with the more-than-additive effect were examined. The enhanced antiproliferation was achieved in HeLa cells as well as H. Ep #2 cells but not in Daudi or M-14 cells, indicating cell dependency of the enhancement. This enhancement was not dependent on the IFN species, including IFN-β, IFN-α (leukocyte), and IFN-α (lymphoblastoid), although the cells were variably sensitive to these IFN species. In contrast, the enhanced antiproliferation was critically dependent on the species of antineoplastic agents, and was selective to VCR and adriamycin among those tested under the present experimental conditions. The sequential exposure of H.Ep #2 cells to IFN and VCR induced the enhancement but exposure to VCR followed by IFN did not, suggesting that IFN-induced cell modification made the cells more sensitive to VCR. Either IFN or VCR was successfully replaced by colchicine, an antimicrotubule agent, but not by cytochalasin D, an antimicrofilament agent, suggesting the involvement of microtubule modification in the enhanced antiproliferation observed with IFN and VCR.