Antiproliferative effects of cytokines on squamous cell carcinoma

• Published in: Archives of otolaryngology--head & neck surgery Vol. 117; no. 3; p. 321
• Main Authors: Sacchi, M, Klapan, I, Johnson, J T, Whiteside, T L
• Format: Journal Article
• Language: English
• Published: United States 01.03.1991
• Subjects: Carcinoma, Squamous Cell - therapy; Cell Division - drug effects; Cell Line; Cytokines - pharmacology; Cytokines - therapeutic use; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Head and Neck Neoplasms - therapy; Interferon Type I - pharmacology; Interferon Type I - therapeutic use; Interferon-gamma - pharmacology; Interferon-gamma - therapeutic use; Recombinant Proteins; Tumor Cells, Cultured - drug effects; Tumor Necrosis Factor-alpha - pharmacology; Tumor Necrosis Factor-alpha - therapeutic use
• ISSN: 0886-4470
• DOI: 10.1001/archotol.1991.01870150089012

A panel of 12 squamous cell carcinoma of the head and neck (SCCHN) cell lines has been used to determine sensitivity of tumor cells to cytokines, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interferon alfa (IFN-alpha) in vitro. Antiproliferative activity of these cytokines on squamous cell carcinoma of the head and neck monolayers was measured in a colorimetric MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide]-based assay. All 12 cell lines tested were sensitive to IFN-gamma, with the 50% inhibitory dose (ID50) ranging from 0.07 +/- 0.001 to 104 +/- 4.6 U/mL. The TNF-alpha showed antiproliferative activity on three cell lines at relatively high doses (ID50 from 55 +/- 4.1 to 847.10 +/- 10 U/mL), and IFN-alpha was growth inhibitory in only one line (ID50 = 1211 +/- 46.2 U/mL). The combination of IFN-gamma and TNF-alpha had a synergistic antiproliferative effect on eight cell lines and an additive effect on two cell lines. In two cell lines, the effect of the combination was equal to that of IFN-gamma alone. A combination of IFN-alpha and TNF-alpha resulted in cell growth inhibition in six of the seven lines tested, and this effect was synergistic. These in vitro studies indicate that combinations of IFN-gamma and TNF-alpha or IFN-alpha and TNF-alpha may be more growth inhibitory against squamous cell carcinoma of the head and neck and at lower doses than each of these cytokines used singly.