Interferon-gamma and cytotoxic agents studied in combination using a soft agarose human tumor clonogenic assay.
The in vitro antiproliferative activity of human recombinant interferon-gamma (IFN-gamma) was tested against human tumor cells in vitro in combination with doxorubicin, cisplatin, or vinblastine. Using a human tumor clonogenic assay (HTCA), IFN-gamma alone showed dose-dependent inhibition of colony growth in six or seven human tumor cell lines as well as in each of nine fresh ovarian tumor specimens. The combination of IFN-gamma and either doxorubicin or cisplatin showed additive antiproliferative effects against all the cell lines with the exception of an IFN-gamma-resistant endometrial cancer cell line (HEC-1A). In combination with vinblastine, IFN-gamma rarely had an additive effect. Inclusion of macrophages from malignant effusions in the HTCA potentiated the antiproliferative effect of IFN-gamma alone as well as the combination of IFN-gamma and doxorubicin; however, the efficacy of the two agents was never more than additive. The results show that combinations of IFN-gamma with doxorubicin or cisplatin are additive and warrant further investigation. The antitumor effect of IFN-gamma alone or in combination with cytotoxic drugs may be significantly enhanced by tumor-associated macrophages.
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002460:Cell Line / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D003114:Colony-Forming Units Assay / Q000379:methods*; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage; D008264:Macrophages / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000188:drug therapy; D012685:Sepharose; D014410:Tumor Stem Cell Assay / Q000379:methods*; D014747:Vinblastine / Q000008:administration & dosage
D014747:Vinblastine; D004317:Doxorubicin; D007371:Interferon-gamma; D012685:Sepharose; D002945:Cisplatin