Cancer Chemotherapy and Pharmacology

, Volume 22, Issue 3, pp 215–222 | Cite as

Effects of scheduling and ascites-associated macrophages on combined antiproliferative activity of alpha-2b interferon and gamma-interferon in a clonogenic assay

  • Junichiro Higashihara
  • Toshiaki Saito
  • Michael E. Berens
  • Charles E. Welander
Original Articles Ascites-Associated Macrophages, α-2b Interferon, λ-Interferon, Clonogenic Assay
Received:
Accepted:

Summary

Effects of combination treatment with human recombinant alpha-2b interferon (IFN-α2b) and gamma interferon (IFN-γ) and sequencing of the combination on colony formation of human tumor cells were studied in a human tumor clonogenic assay (HTCA) with or without ascites-associated macrophages (AAM). Five different human tumor cell lines were studied. Three of the five cell lines (ovarian cancer cell line BG-1, cervical cancer cell line ME-180, and melanoma cell line SK-MEL 28) were sensitive to both IFNs.Cervical cancer cell line CaSki was sensitive to IFN-α2b but resistant to IFN-γ. Endometrial cancer cell line HEC-1A was resistant to both IFNs. Synergistic interaction was observed in BG-1 and SK-MEL 28 with a combination of the IFNs. ME-180 did not exhibit a positive interaction, in spite of its sensitivity to each IFN. CaSki and HEC-1A also did not exhibit a positive combined interaction at clinically achievable concentrations. One sequential combination method (method 1: IFN-α2b → IFN gamma with a 24-h interval) resulted in a similar antitumor effect as the simultaneous combination. A reversed sequential method (method 2: IFN-γ → IFN-α2b with a 24-h interval) was less effective in three of the five cell lines. In BG-1, AAM enclosed in the lower layer markedly enhanced the antitumor effect of combined IFNs as well as each IFN alone. The antitumor effect with method 1 was significantly greater than that achieved with simultaneous combination or combination according to method 2 in the presence of AAM (P<0.01). These results suggest that (1) a synergistic antitumor effect of IFN-α2b and IFN gamma is demonstrable in selected types of tumors, depending upon the sensitivity of each tumor cell line to both IFNs; (2) optimal scheduling for the direct antitumor effect of combined IFNs seems to be long-term exposure of cells to the IFN, the cells being treated with both IFNs either simultaneously or sequentially (IFN-α2b preceding IFN-γ); and (3) AAM potentiate the antitumor effect of IFNs either alone or in combination. Finally, IFN-α2b may have some priming effects for the indirect effect of IFN gamma mediated through AAM in certain tumor cells.

Keywords

Antitumor Effect Endometrial Cancer Cell Endometrial Cancer Cell Line Synergistic Antitumor Effect Simultaneous Combination 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • Junichiro Higashihara
    • 1
  • Toshiaki Saito
    • 1
  • Michael E. Berens
    • 1
  • Charles E. Welander
    • 1
  1. 1.Section on Gynecologic OncologyBowman Gray School of Medicine of Wake Forest UniversityWinston-SalemUSA

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