Osanto S, Jansen R, Vloemans M
Department of Clinical Oncology, Leiden University Hospital, The Netherlands.
Eur J Cancer. 1992;28A(10):1622-7. doi: 10.1016/0959-8049(92)90055-7.
After in vitro incubation of melanoma tumour cells Cmel453A with either recombinant interferon gamma (rIFN-gamma) or tumour necrosis factor alpha (rTNF-alpha) a dose-dependent inhibition of cell growth occurred; when both cytokines were added, a synergistic action was observed. Inhibition of DNA synthesis, as measured by [3H] thymidine incorporation, occurred after 6 h of incubation with rIFN-gamma or rTNF-alpha, and this action was potentiated when the two cytokines were applied simultaneously. Within 1 h, the level of c-myc mRNA in tumour cells had already decreased by, respectively, 60% (S.D. 7) and 25% (S.D. 7); the combined addition of the cytokines resulted in a greater reduction of c-myc mRNA than by each cytokine alone. Downregulation of c-myc expression is an early event, occurring hours before the actual inhibition of outgrowth. Thus, in melanoma cells like Cmel with a high constitutive expression of the c-myc oncogene, the antiproliferative action of rIFN-gamma and rTNF-alpha may be mediated by an inhibition of the expression of c-myc.
将黑色素瘤肿瘤细胞Cmel453A与重组干扰素γ（rIFN-γ）或肿瘤坏死因子α（rTNF-α）进行体外孵育后，出现了细胞生长的剂量依赖性抑制；当同时添加这两种细胞因子时，观察到协同作用。通过[3H]胸苷掺入法测定，与rIFN-γ或rTNF-α孵育6小时后发生DNA合成抑制，当同时应用这两种细胞因子时，这种作用会增强。在1小时内，肿瘤细胞中c-myc mRNA水平分别已经下降了60%（标准差7）和25%（标准差7）；细胞因子联合添加导致c-myc mRNA的减少比单独使用每种细胞因子时更大。c-myc表达的下调是一个早期事件，发生在实际抑制生长之前数小时。因此，在c-myc癌基因组成性高表达的黑色素瘤细胞如Cmel中，rIFN-γ和rTNF-α的抗增殖作用可能是通过抑制c-myc的表达介导的。
