Antiproliferative effects of cytokines on squamous cell carcinoma.
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.
Sacchi
M
M
Department of Otolaryngology, University of Pittsburgh School of Medicine, PA.
Klapan
I
I
Johnson
J T
JT
Whiteside
T L
TL
D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006258:Head and Neck Neoplasms / Q000628:therapy*; D007370:Interferon Type I / Q000494:pharmacology / Q000627:therapeutic use; D007371:Interferon-gamma / Q000494:pharmacology / Q000627:therapeutic use; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000627:therapeutic use
D016207:Cytokines; D007370:Interferon Type I; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma