POSITIVE INTERACTIONS BETWEEN INTERFERON AND CHEMOTHERAPY DUE TO DIRECT TUMOR-ACTION RATHER THAN EFFECTS ON HOST DRUG-METABOLIZING-ENZYMES

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (11) , 5249-5255
Abstract
The mechanism of increased antitumor activity when human lymphoblastoid interferon [HuIFN-.alpha.(Ly)] and the drugs cyclophosphamide and Adriamycin are used in combination on a human tumor xenograft in nude mice was investigated. HuIFN-.alpha.(Ly) did not affect hepatic levels of the drug-metabolizing enzymes cytochrome P-450 or the glutathione S-transferases. In contrast, mouse interferon caused significant and differential changes in the isozymic forms of these enzymes. Addition of mouse interferon to the HuIFN-.alpha.(Ly)/cyclophosphamide or Adriamycin combinations had no effect on the final result and did not increase the toxicity of the combination therapy. The increased activity of the combination therapy evidently is due to effects on the tumor rather than on the host. Further studies showed significant perturbations in the tumor cell cycle after in vivo combination therapy. Cyclophosphamide caused an accumulation in G2 and the addition of HuIFN-.alpha.(Ly), which alone caused little change in cycle distribution, delayed this G2 block and strongly increased the number of cells in S phase. A similar, although less pronounced effect was seen with HuIFN-.alpha.(Ly)/Adriamycin therapy. The increase in S phase seen in combined therapy may account for the synergy seen.

This publication has 15 references indexed in Scilit: