Synergistic Antiproliferative Effect of Human Recombinant Interferons and Retinoic Acid in Cultured Breast Cancer Cells

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Abstract
A combination of retinoic acid (RA) and human recombinant DNA-derived interferon-γ (Hu-IFN-γ) was tested with respect to the growth inhibitory action on several human mammary carcinoma cell lines (ZR-75.1, 734-B, MCF-7, and BT-20), a human lung carcinoma cell line (CCL-185), and a human laryngeal carcinoma cell line (HEP-2). The mammary carcinoma cell lines were all sensitive to Hu-IFN-γ, and 2 of them (ZR-75.1 and 734-B) were also affected by RA. The combination of both substances led to a pronounced synergistic amplification of growth inhibition in ZR-75.1 and 734-B cells. RA also increased the antiproliferative activity of Hu-IFN-γ in the RA-resistant BT-20 cells and to a less pronounced degree in MCF-7 cells. In contrast to these findings, no synergistic effects were observed between Hu-IFN-γ and RA in CCL-185 and HEP-2 cells. Human recombinant DNA-derived interferon-α2 amplified the action of RA only in BT-20 cells, but it did not act synergistically with RA in the other cell lines tested.