Garbe C, Krasagakis K, Zouboulis C C, Schröder K, Krüger S, Stadler R, Orfanos C E
Department of Dermatology, University Medical Center Steglitz, Free University of Berlin, Federal Republic of Germany.
J Invest Dermatol. 1990 Dec;95(6 Suppl):231S-237S. doi: 10.1111/1523-1747.ep12875837.
The antitumor activities of human interferon (IFN) alpha, beta, and gamma alone or in combination were studied on four human melanoma cell lines (StML-11, StML-12, StML-14, and SKMel-28) in various concentrations (1-50,000 IU/ml IFN alpha, 0.1-1000 IU/ml IFN beta, 1-10,000 IU/ml IFN gamma) in vitro. In all experiments IFN beta exhibited the most potent antiproliferative effect of all IFN tested. After 3 d of incubation a 50% growth inhibition was achieved with 20-40 IU/ml for natural IFN beta and with 600-1200 U/ml for recombinant IFN gamma. Substantially higher doses (7,000 to more than 50,000 IU/ml) of recombinant IFN alpha 2a were required to achieve a 50% growth inhibition. A strong synergistic antiproliferative activity resulted from the combination of IFN alpha with IFN gamma and IFN beta with IFN gamma. None of the IFN tested induced terminal differentiation of melanoma cells in vitro. The formation of dendrites was inhibited, and the portion of differentiated cells in vitro was reduced after treatment with IFN in comparison to the untreated controls (untreated controls: 100%; portion of differentiated cells after treatment with IFN alpha: 58%-74%, IFN beta: 48%-96%, IFN gamma: 10%-33%). The melanin synthesis was slightly elevated after treatment with IFN alpha (untreated controls: 100%; after treatment with IFN alpha: 103%-157%, ns.) and decreased significantly after treatment with IFN beta (49%-71%, p less than 0.05) as well as with IFN gamma (80%-88%, ns.). Cell surface markers were modulated varyingly by the IFN: HLA-I antigens were enhanced by all IFN, with IFN beta emerging as the most potent inducer. Only IFN gamma, however, induced a de novo expression of HLA-DR and -DQ antigens and increased the expression of the ICAM-1 molecule and of the melanoma progression marker A.1.43. Possibly, these findings indicate a biologically more aggressive phenotype of melanoma cells.
在体外，研究了人α、β和γ干扰素单独或联合使用对四种人黑色素瘤细胞系（StML-11、StML-12、StML-14和SKMel-28）在不同浓度（1-50,000 IU/ml的α干扰素、0.1-1000 IU/ml的β干扰素、1-10,000 IU/ml的γ干扰素）下的抗肿瘤活性。在所有实验中，β干扰素在所有测试的干扰素中表现出最有效的抗增殖作用。孵育3天后，天然β干扰素20-40 IU/ml以及重组γ干扰素600-1200 U/ml可实现50%的生长抑制。重组α2a干扰素需要更高得多的剂量（7,000至超过50,000 IU/ml）才能实现50%的生长抑制。α干扰素与γ干扰素以及β干扰素与γ干扰素联合使用产生了强烈的协同抗增殖活性。所测试的任何一种干扰素在体外均未诱导黑色素瘤细胞终末分化。树突的形成受到抑制，与未处理的对照相比，用干扰素处理后体外分化细胞的比例降低（未处理对照：100%；用α干扰素处理后分化细胞的比例：58%-74%，β干扰素：48%-96%，γ干扰素：10%-33%）。用α干扰素处理后黑色素合成略有升高（未处理对照：100%；用α干扰素处理后：103%-157%，无显著性差异），而用β干扰素（49%-71%，p<0.05）以及γ干扰素（80%-88%，无显著性差异）处理后黑色素合成显著降低。干扰素对细胞表面标志物的调节各不相同：所有干扰素均增强HLA-I抗原，其中β干扰素是最有效的诱导剂。然而，只有γ干扰素诱导HLA-DR和-DQ抗原的从头表达，并增加ICAM-1分子和黑色素瘤进展标志物A.1.43的表达。这些发现可能表明黑色素瘤细胞具有生物学上更具侵袭性的表型。
